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Genomes and Genes | Robert StroudSummaryAffiliation: University of California Country: USA Publications
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Publications
Architecture and selectivity in aquaporins: 2.5 a X-ray structure of aquaporin ZDavid F Savage
Department of Biochemistry and Biophysics, University of California School of Medicine, San Francisco, California, USA
PLoS Biol 1:E72. 2003....
Cofactor-mediated conformational control in the bifunctional kinase/RNase Ire1Alexei V Korennykh
Howard Hughes Medical Institute, University of California, San Francisco, 600 16th Street, Room S272, Box 0724, San Francisco, CA 94158, USA
BMC Biol 9:48. 2011..In this study, we investigated how the binding of cofactors to the kinase domain of Ire1 modulates its RNase activity...
Structural and functional basis for RNA cleavage by Ire1Alexei V Korennykh
Howard Hughes Medical Institute, University of California, San Francisco, Genentech Hall, 600 16th Street, San Francisco, CA 94158, USA
BMC Biol 9:47. 2011..Here, we experimentally define the active site of Ire1 RNase and quantitatively evaluate the contribution of the key active site residues to catalysis...
Transmembrane transporters: an open and closed caseRobert M Stroud
Department of Biochemistry and Biophysics, University of California, Genentech Hall, 600 16th Street, San Francisco, CA 94158-2517, USA
Proc Natl Acad Sci U S A 104:1445-6. 2007
2007 annual progress report synopsis of the Center for Structures of Membrane ProteinsRobert M Stroud
The Center for Structures of Membrane Proteins CSMP, UCSF, San Francisco, CA 94158 2517, USA
J Struct Funct Genomics 10:193-208. 2009..A synopsis of the 2007 annual progress report for the Center for Structures of Membrane Proteins, a specialized center of the Protein Structure Initiative...
Selectivity and conductance among the glycerol and water conducting aquaporin family of channelsRobert M Stroud
Department of Biochemistry and Biophysics, University of California, San Francisco, CA 94143 2240, USA
FEBS Lett 555:79-84. 2003..Water molecules form a single hydrogen bonded file throughout the 28 A long channel in AqpZ. The basis for absolute exclusion of proton or hydronium ion conductance through the line of water is explored using simulations...
Glycerol facilitator GlpF and the associated aquaporin family of channelsRobert M Stroud
Department of Biochemistry and Biophysics, School of Medicine, 600 16th Street, University of California San Francisco, CA 94143 2240, USA
Curr Opin Struct Biol 13:424-31. 2003..The structure also suggests the mechanism behind the selectivity of aquaglyceroporins for glycerol, the basis for enantioselectivity among alditols, and the basis for the prevention of any leakage of the electrochemical gradient...
Significance of structural changes in proteins: expected errors in refined protein structuresR M Stroud
Department of Biochemistry and Biophysics, University of California San Francisco 94143 0448, USA
Protein Sci 4:2392-404. 1995..Structure change in a macromolecule can thus be referenced to the expected uncertainty in atomic position as reflected in the variance between otherwise identical structures with the observed values of correlated parameters...
Crystal structure of the HIV-1 integrase catalytic core and C-terminal domains: a model for viral DNA bindingJ C Chen
Departments of Biochemistry and Biophysics, Laboratory Medicine, and Internal Medicine, University of California, San Francisco, CA 94143, USA
Proc Natl Acad Sci U S A 97:8233-8. 2000..The crystal structure of the isolated catalytic core domain (residues 52-210), independently determined at 1.6-A resolution, is identical to the core domain within the two-domain 52-288 structure...
Ion-channel-forming colicinsR M Stroud
Department of Biochemistry and Biophysics, University of California, San Francisco School of Medicine 94143 0448, USA
Curr Opin Struct Biol 8:525-33. 1998....
Binding of the anticancer drug ZD1694 to E. coli thymidylate synthase: assessing specificity and affinityE E Rutenber
Department of Biochemistry and Biophysics, University of California at San Francisco, 94143 0448, USA
Structure 4:1317-24. 1996..Attempts to abolish toxicity in human patients while preserving potency against the target enzyme, have led to the development of ZD1694, which has already shown significant activity against colorectal tumours...
Signal sequence recognition and protein targetingR M Stroud
S 960 Department of Biochemistry and Biophysics, School of Medicine, University of California, San Francisco CA 94143 0448, USA
Curr Opin Struct Biol 9:754-9. 1999..The structure of signal peptidase suggests how it releases functional proteins...
On the mechanism of sensing unfolded protein in the endoplasmic reticulumJoel J Credle
Howard Hughes Medical Institute, Departments of Biochemistry and Biophysics and Medicine, University of California, San Francisco, CA 94143-2200, USA
Proc Natl Acad Sci U S A 102:18773-84. 2005..The changes in the ER lumen in turn position Ire1 kinase domains in the cytoplasm optimally for autophosphorylation to initiate the UPR...
Mechanism of ammonia transport by Amt/MEP/Rh: structure of AmtB at 1.35 AShahram Khademi
Department of Biochemistry and Biophysics, S412C Genentech Hall, University of California San Francisco, 600 16th Street, San Francisco, CA 94143 2240, USA
Science 305:1587-94. 2004..Favorable interactions for NH3 are seen within the channel and use conserved histidines. Reconstitution of AmtB into vesicles shows that AmtB conducts uncharged NH3...
The first structure of an RNA m5C methyltransferase, Fmu, provides insight into catalytic mechanism and specific binding of RNA substratePaul G Foster
Department of Biochemistry and Biophysics, University of California San Francisco, San Francisco, CA 94148, USA
Structure 11:1609-20. 2003..Docking of this stem loop RNA into the structure followed by molecular mechanics shows that the Fmu structure is consistent with binding to the folded RNA substrate...
Crystal structure of the priming beta-ketosynthase from the R1128 polyketide biosynthetic pathwayHu Pan
Department of Biophysics and Biochemistry, University of California San Francisco, San Francisco, CA 94143, USA
Structure 10:1559-68. 2002..Selectivity and primer unit size appear to involve the side chains of three residues on the loops close to the dimer interface that constitute the bottom of the substrate binding pocket...
The glycerol facilitator GlpF its aquaporin family of channels, and their selectivityRobert M Stroud
Department of Biochemistry and Biophysics, School of Medicine, University of California, San Francisco, California 94143, USA
Adv Protein Chem 63:291-316. 2003
X-ray structures of the signal recognition particle receptor reveal targeting cycle intermediatesChristopher L Reyes
Graduate Group in Biophysics, Department of Biochemistry and Biophysics, University of California at San Francisco, San Francisco, California, United States of America
PLoS ONE 2:e607. 2007..We propose that these structural changes represent discrete conformational states assumed by FtsY during targeting complex formation and dissociation...
The structure of Cryptococcus neoformans thymidylate synthase suggests strategies for using target dynamics for species-specific inhibitionJanet S Finer-Moore
Department of Biochemistry and Biophysics, University of California, San Francisco, 600 16th Street, Room S412B, San Francisco, CA 94143 2240, USA
Acta Crystallogr D Biol Crystallogr 61:1320-34. 2005..These observations highlight the critical need to incorporate multiple target conformations in any computational attempt to facilitate drug discovery...
A unique RNA Fold in the RumA-RNA-cofactor ternary complex contributes to substrate selectivity and enzymatic functionTom T Lee
Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA 94143, USA
Cell 120:599-611. 2005..Active collaboration of RNA in catalysis leads us to conclude that RumA and its substrate RNA may reflect features from the earliest RNA-protein era...
Unraveling the interface of signal recognition particle and its receptor by using chemical cross-linking and tandem mass spectrometryFeixia Chu
Mass Spectrometry Facility, University of California, San Francisco 94143 0046, USA
Proc Natl Acad Sci U S A 101:16454-9. 2004..FtsY interface in the complex...
Targeting proteins to membranes: structure of the signal recognition particlePascal F Egea
Department of Biochemistry and Biophysics, University of California San Francisco, San Francisco, CA 94143, USA
Curr Opin Struct Biol 15:213-20. 2005....
Structure of a TrmA-RNA complex: A consensus RNA fold contributes to substrate selectivity and catalysis in m5U methyltransferasesAkram Alian
Department of Biochemistry and Biophysics, University of California, San Francisco, CA 94158 2517, USA
Proc Natl Acad Sci U S A 105:6876-81. 2008..Loop residues other than the target U54 make more than half of their hydrogen bonds to the protein via sugar-phosphate moieties, accounting, in part, for the broad consensus sequence for TrmA substrates...
Crystal structure of RumA, an iron-sulfur cluster containing E. coli ribosomal RNA 5-methyluridine methyltransferaseTom T Lee
Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA 94107 USA
Structure 12:397-407. 2004..The iron-sulfur cluster may be involved in the correct folding of the protein or may have a role in RNA binding...
Crystal structure of an RluF-RNA complex: a base-pair rearrangement is the key to selectivity of RluF for U2604 of the ribosomeAkram Alian
Department of Biochemistry and Biophysics, University of California, San Francisco, CA 94158 2517, USA
J Mol Biol 388:785-800. 2009..Residues whose side chains contact rearranged bases in the bound stem-loop, while conserved among RluFs, are not conserved between RluFs and RluBs, suggesting that RluB does not bind to the rearranged stem loop...
Crystal structure of the first KH domain of human poly(C)-binding protein-2 in complex with a C-rich strand of human telomeric DNA at 1.7 AZhihua Du
Department of Pharmaceutical Chemistry, University of California, San Francisco, California 94143 2280, USA
J Biol Chem 280:38823-30. 2005..Interaction of PCBP2 KH1 with the C-rich strand of human telomeric DNA suggests that PCBPs may participate in mechanisms involved in the regulation of telomere/telomerase functions...
Substrate recognition by RNA 5-methyluridine methyltransferases and pseudouridine synthases: a structural perspectiveSun Hur
Department of Biochemistry and Biophysics, University of California, San Francisco, California 94143, USA
J Biol Chem 281:38969-73. 2006
The role of protein dynamics in thymidylate synthase catalysis: variants of conserved 2'-deoxyuridine 5'-monophosphate (dUMP)-binding Tyr-261Zachary Newby
University of California at San Francisco, San Francisco, California 94143 0448, USA
Biochemistry 45:7415-28. 2006..Changes to atomic vibrations in crystals of a ternary complex of Escherichia coli Tyr261Trp are associated with a greater than 2000-fold drop in kcat/Km. These results underline the important contribution of dynamics to catalysis in TS...
Water and glycerol permeation through the glycerol channel GlpF and the aquaporin familyJohn K Lee
Department of Biochemistry and Biophysics, School of Medicine, University of California, San Francisco, CA 94143 2240, USA
J Synchrotron Radiat 11:86-8. 2004..This result reveals the great possibility of emulating and deciphering the function of other aquaporins with GlpF via mutagenesis and investigation of structure and function...
A general protocol for the crystallization of membrane proteins for X-ray structural investigationZachary E R Newby
Department of Biochemistry and Biophysics, University of California in San Francisco, 600 16th Street, San Francisco, California 94158 2517, USA
Nat Protoc 4:619-37. 2009..The process of protein crystallization is highly variable, and obtaining diffraction quality crystals can require weeks to months or even years in some cases...
Structure of human pro-chymase: a model for the activating transition of granule-associated proteasesK Kinkead Reiling
Department of Biochemistry and Biophysics, University of California at San Francisco, San Francisco, California 94143, USA
Biochemistry 42:2616-24. 2003..The zymogen positioning of both the 180s and autolysis loops are synergistic structural elements that appear to prevent premature proteolysis by chymase and, quite possibly, by other dipeptide zymogens...
X-ray crystallographic and NMR studies of protein-protein and protein-nucleic acid interactions involving the KH domains from human poly(C)-binding protein-2Zhihua Du
Department of Pharmaceutical Chemistry, University of California at San Francisco, San Francisco, CA 94158 2517, USA
RNA 13:1043-51. 2007....
Structural context shapes the aquaporin selectivity filterDavid F Savage
Graduate Group in Biophysics, Department of Biochemistry and Biophysics, University of California, San Francisco, CA 94158 2517, USA
Proc Natl Acad Sci U S A 107:17164-9. 2010....
Anisotropic dynamics of the JE-2147-HIV protease complex: drug resistance and thermodynamic binding mode examined in a 1.09 A structureK Kinkead Reiling
Department of Biochemistry and Biophysics, Graduate Group in Biophysics, University of California at San Francisco, San Francisco, California 94143, USA
Biochemistry 41:4582-94. 2002....
Structural basis for conductance by the archaeal aquaporin AqpM at 1.68 AJohn K Lee
Macromolecular Structure Group, Department of Biochemistry and Biophysics, University of California, S 412C Genentech Hall, 600 16th Street, San Francisco, CA 94143 2240, USA
Proc Natl Acad Sci U S A 102:18932-7. 2005..As a result of this and other side-chain substituents in the walls of the channel, the channel is intermediate in size and exhibits differentially tuned electrostatics when compared with the other subfamilies...
Structure of tRNA pseudouridine synthase TruB and its RNA complex: RNA recognition through a combination of rigid docking and induced fitHu Pan
Department of Biophysics and Biochemistry, University of California, San Francisco, CA 94143, USA
Proc Natl Acad Sci U S A 100:12648-53. 2003....
How U38, 39, and 40 of many tRNAs become the targets for pseudouridylation by TruASun Hur
Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA 94143, USA
Mol Cell 26:189-203. 2007....
The channel architecture of aquaporin 0 at a 2.2-A resolutionWilliam E C Harries
Macromolecular Structure Group, Department of Biochemistry and Biophysics, University of California, S 412C Genentech Hall, 600 16th Street, San Francisco, CA 94143 2240, USA
Proc Natl Acad Sci U S A 101:14045-50. 2004..In addition, our structure illustrates the basis for formation of certain types of cataracts that are the result of mutations...
Lessons and conclusions from dissecting the mechanism of a bisubstrate enzyme: thymidylate synthase mutagenesis, function, and structureJanet S Finer-Moore
S-960 Department of Biochemistry and Biophysics, University of California in San Francisco, San Francisco, California 94143-0448, USA
Biochemistry 42:248-56. 2003
Lateral opening of a translocon upon entry of protein suggests the mechanism of insertion into membranesPascal F Egea
Department of Biological Chemistry, University of California, Los Angeles, CA 90095, USA
Proc Natl Acad Sci U S A 107:17182-7. 2010..In vivo, a 15 amino acid truncation of the cytoplasmic C-terminal helix of SecY fails to rescue a secY-deficient strain, supporting the essential role of this helix as suggested from the structure...
Ratiocinative screen of eukaryotic integral membrane protein expression and solubilization for structure determinationFranklin A Hays
Department of Biochemistry and Biophysics, University of California at San Francisco, San Francisco, CA 94158 2517, USA
J Struct Funct Genomics 10:9-16. 2009..A screen of 384 rationally selected eukaryotic IMPs in baker's yeast Saccharomyces cerevisiae is outlined to demonstrate the results expected when applying this discovery-oriented pipeline to whole-organism membrane proteomes...
The crystal structure of E. coli rRNA pseudouridine synthase RluEHu Pan
Department of Biochemistry and Biophysics, University of California at San Francisco, San Francisco, CA 94143, USA
J Mol Biol 367:1459-70. 2007..The stem alone is not a good RluE substrate, suggesting RluE makes additional interactions with other regions in the ribosome...
Crystal structure of the third KH domain of human poly(C)-binding protein-2 in complex with a C-rich strand of human telomeric DNA at 1.6 A resolutionSebastian Fenn
Department of Pharmaceutical Chemistry, University of California, San Francisco, California 94143 2280, USA
Nucleic Acids Res 35:2651-60. 2007..A nucleotide platform, an interesting feature found in some RNA molecules, was identified, evidently for the first time in DNA...
Structures of the signal recognition particle receptor from the archaeon Pyrococcus furiosus: implications for the targeting step at the membranePascal F Egea
Department of Biochemistry and Biophysics, University of California San Francisco, San Francisco, California, USA
PLoS ONE 3:e3619. 2008..Based on previous structures of two sub-complexes, we propose a model of the core of archeal and eukaryotic SRP*SR targeting complexes...
Structural and biochemical insights into the dicing mechanism of mouse Dicer: a conserved lysine is critical for dsRNA cleavageZhihua Du
Departments of Pharmaceutical Chemistry and Biochemistry and Biophysics, University of California, San Francisco, CA 94158 2517, USA
Proc Natl Acad Sci U S A 105:2391-6. 2008..N-terminal residues of this alpha-helix have the potential to engage in minor groove interaction with dsRNA substrates...
The unfolded protein response signals through high-order assembly of Ire1Alexei V Korennykh
Department of Biochemistry and Biophysics, University of California at San Francisco, San Francisco, California 94158, USA
Nature 457:687-93. 2009..Activation of Ire1 through oligomerization expands the mechanistic repertoire of kinase-based signalling receptors...
Conformational dynamics along an enzymatic reaction pathway: thymidylate synthase, "the movie"Robert M Stroud
S-960 Department of Biochemistry and Biophysics, University of California in San Francisco, San Francisco, California 94143-0448, USA
Biochemistry 42:239-47. 2003
Structures of SRP54 and SRP19, the two proteins that organize the ribonucleic core of the signal recognition particle from Pyrococcus furiosusPascal F Egea
Department of Biochemistry and Biophysics, University of California San Francisco, San Francisco, California, USA
PLoS ONE 3:e3528. 2008....
Selecting optimum eukaryotic integral membrane proteins for structure determination by rapid expression and solubilization screeningMin Li
Membrane Protein Expression Center, University of California at San Francisco, San Francisco, CA 94158 2517, USA
J Mol Biol 385:820-30. 2009..This discovery-oriented pipeline provides an efficient way to select proteins from particular membrane protein classes, families, or organisms that may be more suited to structure analysis than others...
Tryptophan 80 and leucine 143 are critical for the hydride transfer step of thymidylate synthase by controlling active site accessTimothy A Fritz
Macromolecular Structure Group, Department of Biochemistry and Biophysics, The University of California San Francisco, San Francisco, California 94143 0448, USA
Biochemistry 41:7021-9. 2002....
The structure of a ketoreductase determines the organization of the beta-carbon processing enzymes of modular polyketide synthasesAdrian T Keatinge-Clay
Department of Biochemistry and Biophysics, University of California, San Francisco, 600 16 th Street, San Francisco, California 94107, USA
Structure 14:737-48. 2006....
Characterization of the 23 S ribosomal RNA m5U1939 methyltransferase from Escherichia coliSanjay Agarwalla
Department of Biochemistry, University of California at San Francisco, San Francisco, California 94143 0448, USA
J Biol Chem 277:8835-40. 2002..We propose to name this gene rumA and accordingly name the protein product as RumA for RNA uridine methyltransferase...
Substrate twinning activates the signal recognition particle and its receptorPascal F Egea
Department of Biochemistry and Biophysics, University of California at San Francisco, California 94143 2240, USA
Nature 427:215-21. 2004..This unique circle of twinned interactions is severed twice on hydrolysis, leading to complex dissociation after cargo delivery...
Redox reactions of the iron-sulfur cluster in a ribosomal RNA methyltransferase, RumA: optical and EPR studiesSanjay Agarwalla
Department of Biochemistry and Biophysics, University of California San Francisco, San Francisco, CA 94107, USA
J Biol Chem 279:34123-9. 2004..Sequence data base searches revealed that RumA homologs are widespread in various kingdoms of life and contain a conserved and unique iron-sulfur cluster binding motif, CX(5)CGGC...
Function of human Rh based on structure of RhCG at 2.1 AFranz Gruswitz
Department of Biochemistry and Biophysics, S412C Genentech Hall, Center for the Structure of Membrane Proteins, and Membrane Protein Expression Center, University of California, San Francisco, CA 94158, USA
Proc Natl Acad Sci U S A 107:9638-43. 2010..Models of the erythrocyte Rh complex based on our RhCG structure suggest that the erythrocytic Rh complex is composed of stochastically assembled heterotrimers of RhAG, RhD, and RhCE...
Structural basis of aquaporin inhibition by mercuryDavid F Savage
Graduate Group in Biophysics, University of California at San Francisco, San Francisco, CA 94158, USA
J Mol Biol 368:607-17. 2007..Thus, we elucidate a steric inhibition mechanism for this important class of channels by mercury...
Mechanism of association and reciprocal activation of two GTPasesShu ou Shan
Department of Biochemistry and Biophysics, University of California, San Francisco, USA
PLoS Biol 2:e320. 2004..Each stage provides a potential control point in the targeting reaction at which regulation by additional components can be exerted, thus ensuring the binding and release of cargo at the appropriate time...
Pyrrolidine carboxamides as a novel class of inhibitors of enoyl acyl carrier protein reductase from Mycobacterium tuberculosisXin He
Department of Pharmaceutical Chemistry, University of California, 600 16 Street, San Francisco, California 94158 2517, USA
J Med Chem 49:6308-23. 2006..Resolution of racemic mixtures of several inhibitors indicate that only one enantiomer is active as an inhibitor of InhA...
Cell-free complements in vivo expression of the E. coli membrane proteomeDavid F Savage
Graduate Group in Biophysics, University of California at San Francisco, San Francisco, California 94158 2517, USA
Protein Sci 16:966-76. 2007..We conclude that CF is a novel, robust expression system capable of expressing more proteins than an in vivo system and suitable for production of membrane proteins at the milligram level...
De novo design of an IL-4 antagonist and its structure at 1.9 ASherry L Laporte
Department of Biochemistry and Biophysics, University of California, 600 16th Street, Box 2240, San Francisco, CA 94143-2240, USA
Proc Natl Acad Sci U S A 102:1889-94. 2005....
Crystal structure of human aquaporin 4 at 1.8 A and its mechanism of conductanceJoseph D Ho
Graduate Program in Chemistry and Chemical Biology and Department of Biochemistry and Biophysics, Genentech Hall, University of California, 600 16th Street, San Francisco, CA 94158 2517, USA
Proc Natl Acad Sci U S A 106:7437-42. 2009....
Crystal structure of bovine mitochondrial factor B at 0.96-A resolutionJohn K Lee
Department of Biochemistry and Biophysics, University of California, San Francisco, CA 94158 2517, USA
Proc Natl Acad Sci U S A 105:13379-84. 2008..Identification of a bound Mg(2+) ion reveals that FB is a metalloprotein. We also report the cocrystal structures of FB bound with phenylarsine oxide and Cd(2+), two known inhibitors of the FB coupling activity...
A survey of integral alpha-helical membrane proteinsLibusha Kelly
Graduate Group in Bioinformatics, University of California at San Francisco, San Francisco, CA, USA
J Struct Funct Genomics 10:269-80. 2009....
Catalytically-active complex of HIV-1 integrase with a viral DNA substrate binds anti-integrase drugsAkram Alian
Department of Biochemistry and Biophysics, University of California, San Francisco, CA 94158, USA
Proc Natl Acad Sci U S A 106:8192-7. 2009..This novel complex may help define substrate interactions and delineate the mechanism of action of known integration inhibitors...
TARP auxiliary subunits switch AMPA receptor antagonists into partial agonistsKaren Menuz
Department of Cellular and Molecular Pharmacology, University of California at San Francisco, San Francisco, CA 94143, USA
Science 318:815-7. 2007..Our results demonstrate that the presence of an auxiliary subunit can determine whether a compound functions as an agonist or antagonist...
Crystal structure of the aquaglyceroporin PfAQP from the malarial parasite Plasmodium falciparumZachary E R Newby
Department of Chemistry, Genentech Hall, School of Medicine, University of California in San Francisco, 600 16th Street, San Francisco, California 94158 2517, USA
Nat Struct Mol Biol 15:619-25. 2008..The two Asn-Pro-Ala (NPA) regions of PfAQP, which bear rare substitutions to Asn-Leu-Ala (NLA) and Asn-Pro-Ser (NPS), participate in preserving the orientation of the selectivity filter asparagines in the center of the channel...
Catalysis, specificity, and ACP docking site of Streptomyces coelicolor malonyl-CoA:ACP transacylaseAdrian T Keatinge Clay
Graduate Group in Biophysics, University of California, San Francisco, San Francisco, CA 94143, USA
Structure 11:147-54. 2003..Macromolecular docking simulations with actinorhodin ACP suggest that the majority of the ACP docking surface is formed by a helical flap. These results should help to engineer polyketide synthases (PKSs) that produce novel polyketides...
An antibiotic factory caught in actionAdrian T Keatinge Clay
Graduate Group in Biophysics, University of California San Francisco, San Francisco, California 94107 2240, USA
Nat Struct Mol Biol 11:888-93. 2004..We provide evidence that the first cyclization of the polyketide occurs within the KS-CLF tunnel. The mechanistic details of this central PKS polymerase could guide biosynthetic chemists in designing new pharmaceuticals and polymers...
The Amt/MEP/Rh family: structure of AmtB and the mechanism of ammonia gas conductionShahram Khademi
Department of Biochemistry and Biophysics, University of California San Francisco, San Francisco, California, USA
Physiology (Bethesda) 21:419-29. 2006..The reprotonation of NH(3) on the receiving side raises the pH on that side in the absence of metabolism of NH(3), and there is no transfer of protons through the protein...
The only active mutant of thymidylate synthase D169, a residue far from the site of methyl transfer, demonstrates the exquisite nature of enzyme specificityDavid L Birdsall
Department of Biochemistry and Biophysics, University of California at San Francisco, San Francisco, CA 94143 0448, USA
Protein Eng 16:229-40. 2003..Changes to partitioning among productive and non-productive conformations of reaction intermediates may contribute as much, if not more, to the diminished activity of this mutant than reduced stabilization of transition states...
The crystal structure of dihydrofolate reductase-thymidylate synthase from Cryptosporidium hominis reveals a novel architecture for the bifunctional enzymeRyan H Lilien
Department of Chemistry, Dartmouth College, Burke Laboratories, Hanover, NH 03755, USA
J Eukaryot Microbiol 50:555-6. 2003
Control of the selectivity of the aquaporin water channel family by global orientational tuningEmad Tajkhorshid
Theoretical Biophysics Group, Beckman Institute, University of Illinois at Urbana Champaign, 405 North Mathews, Urbana, IL 61801, USA
Science 296:525-30. 2002..Both simulations and observations revealed a more regular distribution of channel water and an increased water permeability for the W48F/F200T mutant...
Crystal structure of an Acyl-ACP dehydrogenase from the FK520 polyketide biosynthetic pathway: insights into extender unit biosynthesisKenji Watanabe
Department of Chemical Engineering, Stanford University, Stanford, CA 94305-5025, USA
J Mol Biol 334:435-44. 2003..A biochemical mechanism for the role of FkbI in the biosynthesis of methoxymalonyl-ACP is proposed...
Phylogenetic classification of protozoa based on the structure of the linker domain in the bifunctional enzyme, dihydrofolate reductase-thymidylate synthaseRyan H Lilien
Department of Chemistry, Dartmouth College, Hanover, New Hampshire 03755, USA
J Biol Chem 278:52980-7. 2003..Furthermore, the structure of C. hominis DHFR-TS calls into question surface electrostatic channeling as the universal means of dihydrofolate transport between TS and DHFR in the bifunctional enzyme...
The structural roles of conserved Pro196, Pro197 and His199 in the mechanism of thymidylate synthaseDolores Gonzalez-Pacanowska
Department of Biochemistry and Biophysics, S412-B, University of California San Francisco, San Francisco, CA 94143-0448, USA
Protein Eng 16:607-14. 2003..The small effects of Pro196 or Pro197 mutations on enzyme kinetics suggest that the conformational restrictions encoded by the Pro-Pro sequence are largely maintained when either member of the pair is mutated...
Structural basis for mobility in the 1.1 A crystal structure of the NG domain of Thermus aquaticus FfhUrsula D Ramirez
Department of Molecular Pharmacology and Biological Chemistry, Northwestern University Medical School, 303 E Chicago Avenue, MC S215, Chicago, IL 60611-3008, USA
J Mol Biol 320:783-99. 2002..Our data allows us to propose a structural explanation for the functional significance of sequence elements conserved at the N/G interface...
Crystal structure and molecular modeling of 17-DMAG in complex with human Hsp90Joseph M Jez
Kosan Biosciences, Inc, 3832 Bay Center Place, Hayward, CA 94545, USA
Chem Biol 10:361-8. 2003..We speculate that 17-DMAG analogs constrained to a cis-amide in the ground state could provide a significant increase in affinity for Hsp90...
Structure-based studies on species-specific inhibition of thymidylate synthaseM Paola Costi
Dipartimento di Scienze Farmaceutiche, Universita di Modena e Reggio Emilia, Via G Campi n 183, 41100, Modena, Italy
Biochim Biophys Acta 1587:206-14. 2002..The role of structural and computational studies in the discovery of nonanalog antifolate inhibitors of bacterial TS, naphthalein and dansyl derivatives, and in the understanding of their biological activity profile, are discussed...
Insights into channel architecture and substrate specificity from crystal structures of two macrocycle-forming thioesterases of modular polyketide synthasesShiou Chuan Tsai
Department of Chemical Engineering, Stanford University, Stanford, California 94305 5025, USA
Biochemistry 41:12598-606. 2002..A series of high-resolution snapshots of a protein channel at different pHs is presented alongside analysis of channel residues, which could help in the redesign of the protein channel architecture...
Mechanistic diversity of cytokine receptor signaling across cell membranesRobert M Stroud
Department of Biochemistry and Biophysics, UCSF Genentech Hall, 600 16th Street, University of California, San Francisco, CA 94143-2240, USA
Sci STKE 2004:re7. 2004..The principles uncovered nevertheless illustrate the basis for high specificity and fidelity in cytokine-mediated signaling...
Profile of Robert M. StroudTinsley H Davis
Proc Natl Acad Sci U S A 103:5256-8. 2006
Inhibitory complex of the transmembrane ammonia channel, AmtB, and the cytosolic regulatory protein, GlnK, at 1.96 AFranz Gruswitz
Department of Biochemistry and Biophysics, Genentech Hall, School of Medicine, University of California, 600 16th Street, San Francisco, CA 94158 2517, USA
Proc Natl Acad Sci U S A 104:42-7. 2007..ATP and Mg(2+) augment the interaction of GlnK. The hydrolyzed product, adenosine 5'-diphosphate orients the surface of GlnK for AmtB blockade. 2-Oxoglutarate diminishes AmtB/GlnK association, and sites for 2-oxoglutarate are evaluated...
Research Grants
- RNA Modification Enzymes: Methyltransferase/psi-synthaseRobert M Stroud; Fiscal Year: 2010..The importance of synthase activity is underlined by disorders such as sideroplastic anemia. The RNA MTase is a potential new drug target for anti-HIV therapy. ..
- RNA MODIFICATION ENZYMES:METHYLTRANFERASES/PSI SYNTHASESRobert Stroud; Fiscal Year: 2003..Finally, the work seeks to isolate and characterize a host enzyme that may be a novel target for HIV. ..
- SIGNAL SEQUENCE RECOGNITION AND PROTEIN TARGETINGRobert Stroud; Fiscal Year: 2003..Components of the membrane pore are to be prepared and characterized for structural approaches to translocation. ..
- Molecular Basis for Transmembrane Conduction & SignalingRobert Stroud; Fiscal Year: 2003..A further aim is to improve crystals of the Acetylcholine receptor as a means of three-dimensional structure determination of an archetype of gating mechanisms in an archetype of neuroreceptor superfamilies. ..
- STRUCTURE/FUNCTION OF PROTEINS AT MOLECULAR LEVELRobert Stroud; Fiscal Year: 2002....
- THYMIDYLATE SYNTHASERobert Stroud; Fiscal Year: 2001..b>Robert Stroud, UCSF...
- STRUCTURE BASED DRUG DESIGNRobert Stroud; Fiscal Year: 2004..Public domain access to the structures of therapeutic targets and technology will encourage their use by major pharmaceutical companies for the better design of therapeutics. ..
- RNA Modification Enzymes: Methyltransferase/psi-synthaseRobert Stroud; Fiscal Year: 2004..This is a required enzyme in HIV replication, and as such it may represent a new target for anti-HIV drugs. ..
- SIGNAL SEQUENCE RECOGNITION AND PROTEIN TARGETINGRobert Stroud; Fiscal Year: 2007..These will instruct in the mechanism of replacing the role of RNA by protein, and therefore in the essence of the dynamic roles of SRP RNA and cpSRP43. ..
- Molecular Basis for Transmembrane Conduction & SignalingRobert Stroud; Fiscal Year: 2007..The structures of these proteins will establish their mechanism of action and provide templates for drug discovery aimed at those of particular therapeutic advantage, and the essential elements to understand their selectivity. ..
- Molecular Basis for Transmembrane Conduction & SignalingRobert Stroud; Fiscal Year: 2006..A further aim is to improve crystals of the Acetylcholine receptor as a means of three-dimensional structure determination of an archetype of gating mechanisms in an archetype of neuroreceptor superfamilies. ..
- 2005 Mechanisms of Membrane Transport Gordon ConferenceRobert Stroud; Fiscal Year: 2005..abstract_text> ..
- STRUCTURE BASED DRUG DESIGNRobert Stroud; Fiscal Year: 1999..Public domain access to the structures of therapeutic targets and technology will encourage their use by major pharmaceutical companies for the better design of therapeutics. ..
- STRUCTURE AND FUNCTION OF PROTEINS AT MOLECULAR LEVELRobert Stroud; Fiscal Year: 1980..Preliminary crystallization of a large extra loop (type III) tRNA, which diffracts to approximately 8 A and of tRNA charging enzyme complexes will be pursued in the hope of understanding tRNA plus charging enzyme recognition. ..
- STRUCTURE AND FUNCTION OF PROTEINS AT MOLECULAR LEVELRobert Stroud; Fiscal Year: 1993....
