@article{enriquez_krajewski_strahl_rothbart_dowen_rose_2021, title={Binding specificity and function of the SWI/SNF subunit SMARCA4 bromodomain interaction with acetylated histone}, volume={297}, ISSN={["1083-351X"]}, url={https://doi.org/10.1016/j.jbc.2021.101145}, DOI={10.1016/j.jbc.2021.101145}, abstractNote={Bromodomains (BD) are conserved reader modules that bind acetylated lysine residues on histones. Although much has been learned regarding the in vitro properties of these domains, less is known about their function within chromatin complexes. SWI/SNF chromatin-remodeling complexes modulate transcription and contribute to DNA damage repair. Mutations in SWI/SNF subunits have been implicated in many cancers. Here we demonstrate that the BD of Caenorhabditis elegans SMARCA4/BRG1, a core SWI/SNF subunit, recognizes acetylated lysine 14 of histone H3 (H3K14ac), similar to its Homo sapiens ortholog. We identify the interactions of SMARCA4 with the acetylated histone peptide from a 1.29 Å-resolution crystal structure of the CeSMARCA4 BD-H3K14ac complex. Significantly, most of the SMARCA4 BD residues in contact with the histone peptide are conserved with other proteins containing family VIII bromodomains. Based on the premise that binding specificity is conserved among bromodomain orthologs, we propose that loop residues outside of the binding pocket position contact residues to recognize the H3K14ac sequence. CRISPR-Cas9-mediated mutations in the SMARCA4 BD that abolish H3K14ac binding in vitro had little or no effect on C. elegans viability or physiological function in vivo. However, combining SMARCA4 BD mutations with knockdown of the SWI/SNF accessory subunit PBRM-1 resulted in severe developmental defects in animals. In conclusion, we demonstrated an essential function for the SWI/SNF bromodomain in vivo and detected potential redundancy in epigenetic readers in regulating chromatin remodeling. These findings have implications for the development of small-molecule BD inhibitors to treat cancers and other diseases.}, number={4}, journal={JOURNAL OF BIOLOGICAL CHEMISTRY}, publisher={Elsevier BV}, author={Enriquez, Paul and Krajewski, Krzysztof and Strahl, Brian D. and Rothbart, Scott B. and Dowen, Robert H. and Rose, Robert B.}, year={2021}, month={Oct} }
 @article{buhrman_enriquez_dillard_baer_truong_grunden_rose_2021, title={Structure, Function, and Thermal Adaptation of the Biotin Carboxylase Domain Dimer from Hydrogenobacter thermophilus 2-Oxoglutarate Carboxylase}, volume={60}, ISSN={["0006-2960"]}, url={https://doi.org/10.1021/acs.biochem.0c00815}, DOI={10.1021/acs.biochem.0c00815}, abstractNote={2-Oxoglutarate carboxylase (OGC), a unique member of the biotin-dependent carboxylase family from the order Aquificales, captures dissolved CO2 via the reductive tricarboxylic acid (rTCA) cycle. Structure and function studies of OGC may facilitate adaptation of the rTCA cycle to increase the level of carbon fixation for biofuel production. Here we compare the biotin carboxylase (BC) domain of Hydrogenobacter thermophilus OGC with the well-studied mesophilic homologues to identify features that may contribute to thermal stability and activity. We report three OGC BC X-ray structures, each bound to bicarbonate, ADP, or ADP-Mg2+, and propose that substrate binding at high temperatures is facilitated by interactions that stabilize the flexible subdomain B in a partially closed conformation. Kinetic measurements with varying ATP and biotin concentrations distinguish two temperature-dependent steps, consistent with biotin’s rate-limiting role in organizing the active site. Transition state thermodynamic values derived from the Eyring equation indicate a larger positive ΔH⧧ and a less negative ΔS⧧ compared to those of a previously reported mesophilic homologue. These thermodynamic values are explained by partially rate limiting product release. Phylogenetic analysis of BC domains suggests that OGC diverged prior to Aquificales evolution. The phylogenetic tree identifies mis-annotations of the Aquificales BC sequences, including the Aquifex aeolicus pyruvate carboxylase structure. Notably, our structural data reveal that the OGC BC dimer comprises a “wet” dimerization interface that is dominated by hydrophilic interactions and structural water molecules common to all BC domains and likely facilitates the conformational changes associated with the catalytic cycle. Mutations in the dimerization domain demonstrate that dimerization contributes to thermal stability.}, number={4}, journal={BIOCHEMISTRY}, publisher={American Chemical Society (ACS)}, author={Buhrman, Greg and Enriquez, Paul and Dillard, Lucas and Baer, Hayden and Truong, Vivian and Grunden, Amy M. and Rose, Robert B.}, year={2021}, month={Feb}, pages={324–345} }
 @article{khund-sayeed_he_holzberg_wang_rajagopal_upadhyay_durell_mukherjee_weirauch_rose_et al._2016, title={5-Hydroxymethylcytosine in E-box motifs ACAT|GTG and ACAC|GTG increases DNA-binding of the B-HLH transcription factor TCF4}, volume={8}, ISSN={["1757-9708"]}, DOI={10.1039/c6ib00079g}, abstractNote={We designed a novel method to double-strand Agilent microarrays such that 5mC and 5hmC are incorporated on one DNA strand. Using protein binding microarrays we demonstrate the utility of this method in exploring how cytosine modification outside of CG dinucleotide alter the DNA binding of sequence-specific transcription factors.}, number={9}, journal={INTEGRATIVE BIOLOGY}, author={Khund-Sayeed, Syed and He, Ximiao and Holzberg, Timothy and Wang, Jun and Rajagopal, Divya and Upadhyay, Shriyash and Durell, Stewart R. and Mukherjee, Sanjit and Weirauch, Matthew T. and Rose, Robert and et al.}, year={2016}, pages={936–945} }
 @article{somalinga_buhrman_arun_rose_grunden_2016, title={A High-Resolution Crystal Structure of a Psychrohalophilic alpha-Carbonic Anhydrase from Photobacterium profundum Reveals a Unique Dimer Interface}, volume={11}, ISSN={["1932-6203"]}, url={https://europepmc.org/articles/PMC5148590}, DOI={10.1371/journal.pone.0168022}, abstractNote={Bacterial α-carbonic anhydrases (α-CA) are zinc containing metalloenzymes that catalyze the rapid interconversion of CO2 to bicarbonate and a proton. We report the first crystal structure of a pyschrohalophilic α-CA from a deep-sea bacterium, Photobacterium profundum. Size exclusion chromatography of the purified P. profundum α-CA (PprCA) reveals that the protein is a heterogeneous mix of monomers and dimers. Furthermore, an "in-gel" carbonic anhydrase activity assay, also known as protonography, revealed two distinct bands corresponding to monomeric and dimeric forms of PprCA that are catalytically active. The crystal structure of PprCA was determined in its native form and reveals a highly conserved "knot-topology" that is characteristic of α-CA's. Similar to other bacterial α-CA's, PprCA also crystallized as a dimer. Furthermore, dimer interface analysis revealed the presence of a chloride ion (Cl-) in the interface which is unique to PprCA and has not been observed in any other α-CA's characterized so far. Molecular dynamics simulation and chloride ion occupancy analysis shows 100% occupancy for the Cl- ion in the dimer interface. Zinc coordinating triple histidine residues, substrate binding hydrophobic patch residues, and the hydrophilic proton wire residues are highly conserved in PprCA and are identical to other well-studied α-CA's.}, number={12}, journal={PLOS ONE}, publisher={Public Library of Science (PLoS)}, author={Somalinga, Vijayakumar and Buhrman, Greg and Arun, Ashikha and Rose, Robert B. and Grunden, Amy M.}, editor={Hofmann, AndreasEditor}, year={2016}, month={Dec} }
 @article{lu_yuan_cheng_rose_classen_simmons_2016, title={Modeling the Growth of Archaeon Halobacterium halobium Affected by Temperature and Light}, volume={181}, ISSN={0273-2289 1559-0291}, url={http://dx.doi.org/10.1007/s12010-016-2270-x}, DOI={10.1007/s12010-016-2270-x}, number={3}, journal={Applied Biochemistry and Biotechnology}, publisher={Springer Science and Business Media LLC}, author={Lu, Hao and Yuan, Wenqiao and Cheng, Jay and Rose, Robert B. and Classen, John J. and Simmons, Otto D.}, year={2016}, month={Oct}, pages={1080–1095} }
 @article{friedenberg_buhrman_chdid_olby_olivry_guillaumin_o’toole_goggs_kennedy_rose_et al._2015, title={Evaluation of a DLA-79 allele associated with multiple immune-mediated diseases in dogs}, volume={68}, ISSN={0093-7711 1432-1211}, url={http://dx.doi.org/10.1007/s00251-015-0894-6}, DOI={10.1007/s00251-015-0894-6}, abstractNote={Immune-mediated diseases are common and life-threatening disorders in dogs. Many canine immune-mediated diseases have strong breed predispositions and are believed to be inherited. However, the genetic mutations that cause these diseases are mostly unknown. As many immune-mediated diseases in humans share polymorphisms among a common set of genes, we conducted a candidate gene study of 15 of these genes across four immune-mediated diseases (immune-mediated hemolytic anemia, immune-mediated thrombocytopenia, immune-mediated polyarthritis (IMPA), and atopic dermatitis) in 195 affected and 206 unaffected dogs to assess whether causative or predictive polymorphisms might exist in similar genes in dogs. We demonstrate a strong association (Fisher’s exact p = 0.0004 for allelic association, p = 0.0035 for genotypic association) between two polymorphic positions (10 bp apart) in exon 2 of one allele in DLA-79, DLA-79*001:02, and multiple immune-mediated diseases. The frequency of this allele was significantly higher in dogs with immune-mediated disease than in control dogs (0.21 vs. 0.12) and ranged from 0.28 in dogs with IMPA to 0.15 in dogs with atopic dermatitis. This allele has two non-synonymous substitutions (compared with the reference allele, DLA-79*001:01), resulting in F33L and N37D amino acid changes. These mutations occur in the peptide-binding pocket of the protein, and based upon our computational modeling studies, are likely to affect critical interactions with the peptide N-terminus. Further studies are warranted to confirm these findings more broadly and to determine the specific mechanism by which the identified variants alter canine immune system function.}, number={3}, journal={Immunogenetics}, publisher={Springer Science and Business Media LLC}, author={Friedenberg, Steven G. and Buhrman, Greg and Chdid, Lhoucine and Olby, Natasha J. and Olivry, Thierry and Guillaumin, Julien and O’Toole, Theresa and Goggs, Robert and Kennedy, Lorna J. and Rose, Robert B. and et al.}, year={2015}, month={Dec}, pages={205–217} }
 @article{wang_coco_rose_2015, title={Interactions with the Bifunctional Interface of the Transcriptional Coactivator DCoH1 Are Kinetically Regulated}, volume={290}, ISSN={["1083-351X"]}, DOI={10.1074/jbc.m114.616870}, abstractNote={Pterin-4a-carbinolamine dehydratase (PCD) is a highly conserved enzyme that evolved a second, unrelated function in mammals, as a transcriptional coactivator. As a coactivator, PCD is known as DCoH or dimerization cofactor of the transcription factor HNF-1. These two activities are associated with a change in oligomeric state: from two dimers interacting as an enzyme in the cytoplasm to a dimer interacting with a dimer of HNF-1 in the nucleus. The same interface of DCoH forms both complexes. To determine how DCoH partitions between its two functions, we studied the folding and stability of the DCoH homotetramer. We show that the DCoH1 homotetramer is kinetically trapped, meaning once it forms it will not dissociate to interact with HNF-1. In contrast, DCoH2, a paralog of DCoH1, unfolds within hours. A simple mutation in the interface of DCoH2 from Ser-51 to Thr, as found in DCoH1, increases the kinetic stability by 9 orders of magnitude, to τ(½) ∼ 2 million years. This suggests that the DCoH1·HNF-1 complex must co-fold to interact. We conclude that simple mutations can dramatically affect the dissociation kinetics of a complex. Residue 51 represents a "kinetic hot spot" instead of a "thermodynamic hot spot." Kinetic regulation allows PCD to adopt two distinct functions. Mutations in DCoH1 associated with diabetes affect both functions of DCoH1, perhaps by disrupting the balance between the two DCoH complexes.}, number={7}, journal={JOURNAL OF BIOLOGICAL CHEMISTRY}, author={Wang, Dongli and Coco, Matthew W. and Rose, Robert B.}, year={2015}, month={Feb}, pages={4319–4329} }
 @article{golla_zhao_mann_sayeed_mandal_rose_vinson_2014, title={Carboxylation of cytosine (5caC) in the CG dinucleotide in the E-box motif (CGCAG vertical bar GTG) increases binding of the Tcf3 vertical bar Ascl1 helix-loop-helix heterodimer 10-fold}, volume={449}, ISSN={["1090-2104"]}, DOI={10.1016/j.bbrc.2014.05.018}, abstractNote={Three oxidative products of 5-methylcytosine (5mC) occur in mammalian genomes. We evaluated if these cytosine modifications in a CG dinucleotide altered DNA binding of four B-HLH homodimers and three heterodimers to the E-Box motif CGCAG|GTG. We examined 25 DNA probes containing all combinations of cytosine in a CG dinucleotide and none changed binding except for carboxylation of cytosine (5caC) in the strand CGCAG|GTG. 5caC enhanced binding of all examined B-HLH homodimers and heterodimers, particularly the Tcf3|Ascl1 heterodimer which increased binding ~10-fold. These results highlight a potential function of the oxidative products of 5mC, changing the DNA binding of sequence-specific transcription factors.}, number={2}, journal={BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS}, author={Golla, Jaya Prakash and Zhao, Jianfei and Mann, Ishminder K. and Sayeed, Syed K. and Mandal, Ajeet and Rose, Robert B. and Vinson, Charles}, year={2014}, month={Jun}, pages={248–255} }
 @article{babin_wang_rose_sagui_2013, title={Binding Polymorphism in the DNA Bound State of the Pdx1 Homeodomain}, volume={9}, ISSN={["1553-7358"]}, DOI={10.1371/journal.pcbi.1003160}, abstractNote={The subtle effects of DNA-protein recognition are illustrated in the homeodomain fold. This is one of several small DNA binding motifs that, in spite of limited DNA binding specificity, adopts crucial, specific roles when incorporated in a transcription factor. The homeodomain is composed of a 3-helix domain and a mobile N-terminal arm. Helix 3 (the recognition helix) interacts with the DNA bases through the major groove, while the N-terminal arm becomes ordered upon binding a specific sequence through the minor groove. Although many structural studies have characterized the DNA binding properties of homeodomains, the factors behind the binding specificity are still difficult to elucidate. A crystal structure of the Pdx1 homeodomain bound to DNA (PDB 2H1K) obtained previously in our lab shows two complexes with differences in the conformation of the N-terminal arm, major groove contacts, and backbone contacts, raising new questions about the DNA recognition process by homeodomains. Here, we carry out fully atomistic Molecular Dynamics simulations both in crystal and aqueous environments in order to elucidate the nature of the difference in binding contacts. The crystal simulations reproduce the X-ray experimental structures well. In the absence of crystal packing constraints, the differences between the two complexes increase during the solution simulations. Thus, the conformational differences are not an artifact of crystal packing. In solution, the homeodomain with a disordered N-terminal arm repositions to a partially specific orientation. Both the crystal and aqueous simulations support the existence of different stable binding conformers identified in the original crystallographic data with different degrees of specificity. We propose that protein-protein and protein-DNA interactions favor a subset of the possible conformations. This flexibility in DNA binding may facilitate multiple functions for the same transcription factor.}, number={8}, journal={PLOS COMPUTATIONAL BIOLOGY}, author={Babin, Volodymyr and Wang, Dongli and Rose, Robert B. and Sagui, Celeste}, year={2013}, month={Aug} }
 @article{lu_guanga_wan_rose_2012, title={A Novel DNA Binding Mechanism for maf Basic Region-Leucine Zipper Factors Inferred from a MafA-DNA Complex Structure and Binding Specificities}, volume={51}, ISSN={["0006-2960"]}, DOI={10.1021/bi301248j}, abstractNote={MafA is a proto-oncoprotein and is critical for insulin gene expression in pancreatic β-cells. Maf proteins belong to the AP1 superfamily of basic region-leucine zipper (bZIP) transcription factors. Residues in the basic helix and an ancillary N-terminal domain, the Extended Homology Region (EHR), endow maf proteins with unique DNA binding properties: binding a 13 bp consensus site consisting of a core AP1 site (TGACTCA) flanked by TGC sequences and binding DNA stably as monomers. To further characterize maf DNA binding, we determined the structure of a MafA-DNA complex. MafA forms base-specific hydrogen bonds with the flanking G(-5)C(-4) and central C(0)/G(0) bases, but not with the core-TGA bases. However, in vitro binding studies utilizing a pulse-chase electrophoretic mobility shift assay protocol revealed that mutating either the core-TGA or flanking-TGC bases dramatically increases the binding off rate. Comparing the known maf structures, we propose that DNA binding specificity results from positioning the basic helix through unique phosphate contacts. The EHR does not contact DNA directly but stabilizes DNA binding by contacting the basic helix. Collectively, these results suggest a novel multistep DNA binding process involving a conformational change from contacting the core-TGA to contacting the flanking-TGC bases.}, number={48}, journal={BIOCHEMISTRY}, author={Lu, Xun and Guanga, Gerald P. and Wan, Cheng and Rose, Robert B.}, year={2012}, month={Dec}, pages={9706–9717} }
 @article{martin_guenther_sit_swartz_meilleur_lommel_rose_section_2010, title={Crystallization and preliminary X-ray diffraction analysis of red clover necrotic mosaic virus}, volume={66}, ISSN={["2053-230X"]}, url={http://europepmc.org/abstract/med/21045294}, DOI={10.1107/s1744309110032483}, abstractNote={Red clover necrotic mosaic virus (RCNMV) is a species that belongs to the Tombusviridae family of plant viruses with a T = 3 icosahedral capsid. RCNMV virions were purified and were crystallized for X-ray analysis using the hanging-drop vapor-diffusion method. Self-rotation functions and systematic absences identified the space group as I23, with two virions in the unit cell. The crystals diffracted to better than 4 Å resolution but were very radiation-sensitive, causing rapid decay of the high-resolution reflections. The data were processed to 6 Å in the analysis presented here.}, number={Pt 11}, journal={ACTA CRYSTALLOGRAPHICA SECTION F-STRUCTURAL BIOLOGY COMMUNICATIONS}, author={Martin, S.L. and Guenther, R.H. and Sit, T.L. and Swartz, P.D. and Meilleur, Flora and Lommel, S.A. and Rose, Robert and Section, F.}, year={2010}, month={Nov}, pages={1458–1462} }
 @article{rho_jones_rose_2010, title={Kinetic Stability May Determine the Interaction Dynamics of the Bifunctional Protein DCoH1, the Dimerization Cofactor of the Transcription Factor HNF-1 alpha}, volume={49}, ISSN={["0006-2960"]}, DOI={10.1021/bi1015056}, abstractNote={The two disparate functions of DCoH1 (dimerization cofactor of HNF-1)/PCD (pterin-4a-carbinolamine dehydratase) are associated with a change in oligomeric state. DCoH dimers enhance the activity of the diabetes-associated transcription factor HNF-1α (hepatocyte nuclear factor-1α), while the PCD activity of DCoH1 homotetramers aids in aromatic amino acid metabolism. These complexes compete for the same interface of the DCoH dimer. Formation of the DCoH1/HNF-1α complex requires cofolding. The homotetramer of the DCoH1 paralogue, DCoH2, interacts with HNF-1α through simple mixing. To further investigate regulation of DCoH/HNF-1α complex formation, we measured the stability of the DCoH1 homotetramer through unfolding studies by intrinsic tryptophan fluorescence. DCoH2 unfolding is reversible. Surprisingly, the DCoH1 homotetramer is resistant to guanidine unfolding but refolds at a much lower guanidine concentration. We show that a point mutation at the DCoH1 tetramer interface, Thr 51 Ser, overcomes the dissociation barrier of the homotetramer and increases the interaction with HNF-1α. The 1.8 Ǻ resolution crystal structure of DCoH1 T51S shows the presence of an ordered water molecule at the tetramer interface, as in DCoH2, which may destabilize the homotetramer. The equilibrium unfolding data were fit to a two-state model with no apparent intermediate. Folding intermediates were detectable by size exclusion chromatography. For wild-type DCoH1 the intermediates changed with time, suggesting a kinetic origin for the unfolding barrier of the homotetramer. We propose an unfolding pathway in which the tetramer unfolds slowly, but the dimer folds reversibly. Implications for regulation of DCoH1/HNF-1α complex formation are discussed.}, number={47}, journal={BIOCHEMISTRY}, author={Rho, H. and Jones, C. N. and Rose, R. B.}, year={2010}, month={Nov}, pages={10187–10197} }
 @article{serrano_davis_gaff_zhang_chen_d'antonio_bowden_rose_franzen_2010, title={X-ray structure of the metcyano form of dehaloperoxidase from Amphitrite ornata: Evidence for photoreductive dissociation of the iron-cyanide bond}, volume={66}, journal={Acta Crystallographica. Section D, Biological Crystallography}, author={Serrano, V. S. and Davis, M. F. and Gaff, J. F. and Zhang, Q. and Chen, Z. and D'Antonio, E. L. and Bowden, E. F. and Rose, R. and Franzen, S.}, year={2010}, pages={770–782} }
 @article{longo_guanga_rose_2008, title={Crystal structure of E47 neuroD1/Beta2 bHLH domain DNA complex: Heterodimer selectivity and DNA recognition}, volume={47}, ISSN={["0006-2960"]}, DOI={10.1021/bi701527r}, abstractNote={The ubiquitous class I basic helix−loop−helix (bHLH) factor E47 forms heterodimers with multiple tissue specific class II bHLH proteins to regulate distinct differentiation pathways. In order to define how class I− class II heterodimer partners are selected, we determined the crystal structure of the E47−NeuroD1-bHLH dimer in complex with the insulin promoter E-box sequence. Purification of the bHLH domain of E47−NeuroD1 indicates that E47 heterodimers are stable in solution. The interactions between E47 and NeuroD1 in the heterodimer are comparable to the interactions between E47 monomers in the homodimer, including hydrogen bonding, buried hydrophobic surface, and packing interactions. This is consistent with a model in which E47−NeuroD1 heterodimers are favored due to the instability of NeuroD1 homodimers. Although E47−NeuroD1 is oriented uniquely on the E-box sequence (CATCTG) within the promoter of the insulin gene, no direct contacts are observed with the central base pairs within this E-box sequence. We propose that concerted domain motions allow E47 to form specific base contacts in solution. NeuroD1 is restrained from adopting the same base contacts by an additional phosphate backbone interaction by the neurogenic-specific residue His115. Orienting E47−NeuroD1 on promoters may foster protein−protein contacts essential to initiate transcription.}, number={1}, journal={BIOCHEMISTRY}, author={Longo, Antonella and Guanga, Gerald P. and Rose, Robert B.}, year={2008}, month={Jan}, pages={218–229} }
 @article{longo_guanga_rose_2007, title={Structural Basis for Induced Fit Mechanisms in DNA Recognition by the Pdx1 Homeodomain†,‡}, volume={46}, ISSN={0006-2960 1520-4995}, url={http://dx.doi.org/10.1021/bi060969l}, DOI={10.1021/bi060969l}, abstractNote={Pancreatic and duodenal homeobox 1 (Pdx1) is a homeodomain transcription factor belonging to the ParaHox family. Pdx1 plays an essential role in pancreatic endocrine and exocrine cell development and maintenance of adult islet β-cell function. Mutations in the human pdx1 gene are linked to an early onset form of non-insulin-dependent diabetes mellitus, MODY-4. We demonstrate that the homeodomain reproduces the binding specificity of the full-length protein. We report the 2.4 Å resolution crystal structure of the homeodomain bound to a target DNA. The two Pdx1/DNA complexes in the asymmetric unit display conformational differences: in the DNA curvature, the orientation of the homeodomain in the major groove, and the order of the N-terminal arm. Comparing the two complexes indicates invariant protein−DNA contacts, and variant contacts that are unique to each binding orientation. An induced fit model is proposed that depends on the DNA conformation and provides a mechanism for nonlocal contributions to binding specificity.}, number={11}, journal={Biochemistry}, publisher={American Chemical Society (ACS)}, author={Longo, Antonella and Guanga, Gerald P. and Rose, Robert B.}, year={2007}, month={Mar}, pages={2948–2957} }
 @article{longo_guanga_rose_2007, title={Structural basis for induced fit mechanisms in DNA recognition by the Pdx1 homeodomain}, volume={46}, DOI={10.1021/bi0609691}, number={11}, journal={Biochemistry}, author={Longo, A. and Guanga, G. P. and Rose, Robert}, year={2007}, pages={2948–2957} }
 @article{wan_tempel_liu_wang_rose_2005, title={Structure of the conserved transcriptional repressor enhancer of rudimentary homolog}, volume={44}, ISSN={["0006-2960"]}, DOI={10.1021/bi047785w}, abstractNote={erh (enhancer of rudimentary homolog) is a ubiquitously expressed transcriptional coregulator that is highly conserved among eukaryotes, from humans to plants to protozoa. Functions attributed to erh include enhancement of pyrimidine biosynthesis, a role in cell cycle regulation, and repression of the tissue-specific transcription factor HNF-1 (hepatocyte nuclear factor-1) through binding the coactivator DCoH (dimerization cofactor of HNF1). No homologous sequences, other than erh orthologs, have been identified, and little is known about the interactions of erh. To further elucidate its function, we determined the crystal structure of erh to 2.0 A resolution. The erh structure is a novel alpha + beta fold consisting of a four-stranded antiparallel beta sheet with three amphipathic alpha helices situated on one face of the beta sheet. Structure-based searches of the Protein Data Bank, like sequence-based searches, failed to identify paralogs. We present structural and biochemical evidence that erh functions as a dimer. The dimer interface consists of a beta sandwich composed of the beta sheet from each monomer. Many of the surface residues of erh are conserved, including patches of hydrophobic and charged residues, suggesting protein-protein interaction interfaces. Two putative CKII phosphorylation sites are highly ordered in the structure and are predicted to disrupt dimerization and protein-protein interactions.}, number={13}, journal={BIOCHEMISTRY}, author={Wan, C and Tempel, W and Liu, ZJ and Wang, BC and Rose, RB}, year={2005}, month={Apr}, pages={5017–5023} }
 @article{rose_pullen_bayle_crabtree_alber_2004, title={Biochemical and structural basis for partially redundant enzymatic and ranscriptional functions of DCoH and DCoH2}, volume={43}, ISSN={["0006-2960"]}, DOI={10.1021/bi049620t}, abstractNote={An inherited form of diabetes, maturity-onset diabetes of the young type 3 (MODY3), results from mutations in the transcriptional activator, hepatocyte nuclear factor-1α (HNF1α). Transcription by HNF1α is stimulated by the bifunctional coactivator DCoH (dimerization cofactor of HNF1). Strikingly, an HNF1α deletion in mice causes more severe phenotypes than a DCoH deletion. It has been hypothesized that a DCoH homolog, DCoH2, partially complements the DCoH deletion. To test this idea, we determined the biochemical properties and the 1.6-Å-resolution crystal structure of DCoH2. Like DCoH, DCoH2 forms a tetramer, displays pterin-4α-carbinolamine dehydratase activity, and binds HNF1α in vivo and in vitro. DCoH and DCoH2 adopt identical folds with structural differences confined largely to the protein surfaces and the tetramer interface. In contrast to the hyperstable DCoH tetramer, DCoH2 readily disproportionates and forms a 2:2 complex with HNF1 in vitro. Phylogenetic analysis reveals six major subfamilies of DCoH proteins, including unique DCoH and DCoH2 branches in metazoans. These results suggest distinct roles for DCoH and DCoH2. Differences in conserved surface residues could mediate binding to different effectors. We propose that HNF1α binding kinetics may distinguish regulation by DCoH2, under thermodynamic control, from regulation by DCoH, under kinetic control.}, number={23}, journal={BIOCHEMISTRY}, author={Rose, RB and Pullen, KE and Bayle, JH and Crabtree, GR and Alber, T}, year={2004}, month={Jun}, pages={7345–7355} }
 @article{rose_craik_stroud_1998, title={Domain flexibility in retroviral proteases: structural implications for drug resistant mutations.}, url={https://doi.org/10.1021/bi9716074}, DOI={10.1021/bi9716074}, abstractNote={Rigid body rotation of five domains and movements within their interfacial joints provide a rational context for understanding why HIV protease mutations that arise in drug resistant strains are often spatially removed from the drug or substrate binding sites. Domain motions associated with substrate binding in the retroviral HIV-1 and SIV proteases are identified and characterized. These motions are in addition to closure of the flaps and result from rotations of approximately 6-7 degrees at primarily hydrophobic interfaces. A crystal structure of unliganded SIV protease (incorporating the point mutation Ser 4 His to stabilize the protease against autolysis) was determined to 2.0 A resolution in a new space group, P3221. The structure is in the most "open" conformation of any retroviral protease so far examined, with six residues of the flaps disordered. Comparison of this and unliganded HIV structures, with their respective liganded structures by difference distance matrixes identifies five domains of the protease dimer that move as rigid bodies against one another: one terminal domain encompassing the N- and C-terminal beta sheet of the dimer, two core domains containing the catalytic aspartic acids, and two flap domains. The two core domains rotate toward each other on substrate binding, reshaping the binding pocket. We therefore show that, for enzymes, mutations at interdomain interfaces that favor the unliganded form of the target active site will increase the off-rate of the inhibitor, allowing the substrate greater access for catalysis. This offers a mechanism of resistance to competitive inhibitors, especially when the forward enzymatic reaction rate exceeds the rate of substrate dissociation.}, journal={Biochemistry}, author={Rose, RB and Craik, CS and Stroud, R. M.}, year={1998}, month={Feb} }
 @article{rose_craik_douglas_stroud_1996, title={Three-dimensional structures of HIV-1 and SIV protease product complexes.}, url={https://doi.org/10.1021/bi9612733}, DOI={10.1021/bi9612733}, abstractNote={Strain is eliminated as a factor in hydrolysis of the scissile peptide bond by human immunodeficiency virus (HIV)-1 and simian immunodeficiency virus (SIV), based on the first eight complexes of products of hydrolysis with the enzymes. The carboxyl group generated at the scissile bond interacts with both catalytic aspartic acids. The structures directly suggest the interactions of the gemdiol intermediate with the active site. Based on the structures, the nucleophilic water is displaced stereospecifically by substrate binding toward one catalytic aspartic acid, while the scissile carbonyl becomes hydrogen bonded to the other catalytic aspartic acid in position for hydrolysis. Crystal structures for two N-terminal (P) products and two C-terminal (Q) products provide unambiguous density for the ligands at 2.2-2.6 A resolution and 17-21% R factors. The N-terminal product, Ac-S-L-N-F/, overlaps closely with the N-terminal sequences of peptidomimetic inhibitors bound to the protease. Comparison of the two C-terminal products, /F-L-E-K and /F(NO2)-E-A-Nle-S, indicates that the P2' residue is highly constrained, while the positioning of the P1' and P3' residues are sequence dependent.}, journal={Biochemistry}, author={Rose, RB and Craik, CS and Douglas, NL and Stroud, R. M.}, year={1996}, month={Oct} }
 @article{rose_salto_craik_stroud_1993, title={Structure of the protease from simian immunodeficiency virus: complex with an irreversible nonpeptide inhibitor.}, url={https://doi.org/10.1021/bi00097a030}, DOI={10.1021/bi00097a030}, abstractNote={ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTStructure of the protease from simian immunodeficiency virus: Complex with an irreversible nonpeptide inhibitorRobert B. Rose, Jason R. Rose, Rafael Salto, Charles S. Craik, and Robert M. StroudCite this: Biochemistry 1993, 32, 46, 12498–12507Publication Date (Print):November 1, 1993Publication History Published online1 May 2002Published inissue 1 November 1993https://doi.org/10.1021/bi00097a030RIGHTS & PERMISSIONSArticle Views125Altmetric-Citations26LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (3 MB) Get e-Alerts Get e-Alerts}, journal={Biochemistry}, author={Rose, RB and Salto, R and Craik, CS and Stroud, RM}, year={1993}, month={Nov} }