1996–1999

1999

Expression, purification, and structural characterization of the bacteriorphodopsin aspartyl transcarbamylase fusion protein.
Turner, G.J., Miercke, L.J.W., Mitra, A.K., Stroud, R.M., Betlach, M.C., Winter-Vann, A. (1999).
Protein Expression and Purification 17, 324-338.
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Conserved phosphate-binding arginines in thymidylate synthase: Mutations of Arg 178, but not Arg 179 or Arg 23, destabilize the phosphate binding site and impair dump binding.
Finer-Moore, JS; Fauman, EB; Morse, RJ; Santi, DV; Stroud, RM. (1999)
To be published
PDB Accession Nos 1BO7, 1BO8, 1BPO, 1BP6, and 1BPJ
View PDB structure 1BO7, 1BO8, 1BP0, 1BP6, 1BPJ

The structural mechanism for half-the-sites reactivity in an enzyme, thymidylate synthase, involves a relay of changes between subunits.
Anderson, AC; O'Neil, RH; Delano, WL; and Stroud, RM. (1999)
Biochemistry 38, 13829-13836
PDB Accession No. 1CI7
Review abstract
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Functional changes in the structure of the SRP GTPase on binding GDP and Mg2;+ GDP.
Freyman, DM; Keenan, RJ; Stroud, RM; and Walter, P. (1999)
Nature Structural Biology 6, 793-801.
PDB Accession Nos. 1NG1, 2NG1 , 3NG1
Review abstract
View PDB structure 1NG1, 2NG1, 3NG1
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Engineering a soluble extracellular erythropoietin receptor (EPObp) in Pichia pastoris to eliminate microheterogeneity, and its complex with erythropoietin.
Zhan, H; Liu, B; Reid, SW; Aoki, KH; Li, C; Syed, RS; Karkaria, C; Koe, G; Sitney, K; Hayenga, K; Mistry, F; Savel, L; Dreyer, M; Katz, BA; Schreurs, J; Matthews, DJ; Cheetham, JC; Egrie, J; Giebel, LB; Stroud, RM. (1999)
Protein Engineering 12, 505-513.
Review abstract
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Phthalein derivatives as a new tool for selectivity in thymidylate synthase inhibition.
Costi, MP; Rinaldi, M; Tondi, D; Pecorari, P; Barlocco, D; Ghelli, S; Stroud, RM; Santi, DV; Stout, TJ; Musiu, C; Marangiu, EM; Pani, A; Congiu, D; Loi, GA; and La Colla, P. (1999)
Journal of Medicinal Chemistry 42, 2112-2124.
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Structure-based design of inhibitors specific for bacterial thymidylate synthase.
Stout, TJ; Tondi, D; Rinaldi, M; Barlocco, D; Pecorari, P; Santi, DV; Kuntz, ID; Stroud, RM; Shoichet, BK; and Costi, MP. (1999)
Biochemistry 38, 1607-1617
PDB Accession Nos: 1TSL (LcTS with compound 4) , 1TSM (LcTS with compound 5).
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Review abstract
View PDB structure 1TSL, 1TSM

Signal Sequence Recognition and Protein Targeting.
Stroud, R.M. and Walter, P. (1999).
Current Opinion in Structural Biology 9: 754-759.
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1998

Ion-channel-forming colicins.
Stroud, RM; Reiling, K; Wiener, M; Freymann, D. (1998)
Current Opinion in Structural Biology 8, 525-533.
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Efficiency of signalling through cytokine receptors depends critically on receptor orientation.
Syed, RS; Reid, SW; Li, C; Cheetham, JC; Aoki, KH; Liu, B;  Zhan, H; Osslund, TD; Chirino, AJ; Zhang, J; Finer-Moore, J; Elliot, S;  Sitney, K; Katz, BA; Matthews, DJ; Wendoloski, JJ; Egrie, J; and Stroud, RM. (1998)
Nature 395, 511-516
PDB Accession No.1CN4 (replaced 1BLW)
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Review abstract
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Discovery of thymidylate synthase inhibitors using flexible docking and an empirically tuned scoring function.
Welch, W; Sage, CR;  Stout, TJ; Klein, T; Ruppert, J; Stroud, RM; Jain, A. (1998)
To be published
PDB Accession No. 1AXW
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Helical protein design.
Schafmeister, CE; Stroud, RM. (1998)
Current Opinion in Biotechnology 9, 350-353.
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D221 in thymidylate synthase controls conformation change, and thereby opening of the imidazolidine.
Sage, CR; Michelitsch, MD; Stout, TJ; Biermann, D; Nissen, R; Finer-Moore, J; Stroud, RM. (1998)
Biochemistry 37, 13893-13901.
PDB Accession Nos: 1BJG  (D169N with FdUMP , CH2H4folate); 1DNA (D169N with dUMP , CB3717).
View PDB structure 1BJG, 1DNA 
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Crystal structures of a unique thermal-stable thymidylate synthase from Bacillus subtilis.
Stout, TJ; Schellenberger, U; Santi, DV; Stroud, RM. (1998)
Biochemistry 37, 14736-14747.
PDB Accession Numbers:1BKP for bsTS-I, 1BKO for bsTS-II,  1BSP for bsTS-III,  and 1BSF for bsTS-IV.
View PDB structure 1BKP, 1BKO, 1BSP, 1BSF
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The additivity of substrate fragments in enzyme-ligand binding.
Stout, TJ; Sage, CR; Stroud, RM. (1998)
Structure 6, 839-848.
PDB Accession Numbers:1TJS for apo-TS, 1BID for binaryTS + dUMP, 1BDU for binaryTS +dUrd + PO4,sup2; -, 1AOB for binaryTS + ddUrd + PO4,sup2; -, 1KCE for ternary TS + CB3717 + dUMP, 1TDU for ternary TS + CB3717 + dUrd + PO4, sup2; -, 1DDU for ternary TS + CB3717 + ddUrd + PO4,sup2; -, 1AN5 for ternary TS + CB3717 + PO4,sup2; -.
View PDB structure 1TJS, 1BID, 1BDU, 1AOB, 1KCE, 1TDU, 1DDU, 1AN5

Inactivity of N229A thymidylate synthase due to water mediated effects: Isolating a late stage in methyl transfer.
Reyes, CL; Sage, CR; Rutenber, EE; Nissen, R; Stroud, RM; Finer-Moore JS. (1998).
Journal of Molecular Biology 284, 699-712.
PDB Accession Nos:1BQ1 for ternary N229(177)A, 1BQ2 for binary N229(177)A.
View PDB structure 1BQ1, 1BQ2  
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The separate effects of E60Q in Lactobacillus casei thymidylate synthase delineate between mechanisms for formation of intermediates in catalysis.
Birdsall, DL; Huang, W; Santi, DV; Stroud, RM; Finer-Moore, J. (1998)
Protein Engineering 11, 171-183.  
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Crystal structure of the signal sequence binding subunit of the signal recognition particle.
Keenan, RJ; Freymann, DM; Walter, P; Stroud, RM. (1998)
Cell 94, 181-191.
PDB Accession No. 2FFH
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Review abstract
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Structure of bovine pancreatic cholesterol esterase at 1.6 Å: Novel structural features involved in lipase activation.
Chen, C-H; Miercke, LJW; Krucinski, J; Starr, JR; Saenz, G; Wang, X; Spilburg, CA; Lange, LG; Ellsworth, JL; Stroud, RM. (1998)
Biochemistry 37, 5107-5117.
PDB Accession No. 2BCE
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Design of potent selective zinc-mediated serine protease inhibitors. 
Katz, BA; Clark, JM; Finer-Moore, JS; Jenkins, TE; Johnson, CR; Ross, MJ; Luong, C; Moore, WR; Stroud, RM. (1998)
Nature 391, 608-612.
PDB Accession Nos.: 1XUF, 1XUG, 1XUH, 1XUI, 1XUJ , 1XUK.
Review abstract 
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View PDB structure 1XUF, 1XUG, 1XUH, 1XUI, 1XUJ, 1XUK 

Domain flexibility in retroviral proteases: structural implications for drug resistant mutations.
Rose, RB; Craik, CS; Stroud, RM. (1998)
Biochemistry 37, 2607-2621
PDB Accession No. 1AZ5
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Contributions of orientation and hydrogen bonding to catalysis in Asn229 mutants of thymidylate synthase.
Finer-Moore, JS; Liu, L; Birdsall, DL; Brem, R; Apfeld, J; Santi, DV; Stroud, RM. (1998)
Journal of Molecular Biology 276, 113-129.
PDB Accession Nos: 1JMF, 1JMG, 1JMH, 1JMI, 1TVU, 1TVV , 1TVW.
View PDB structure 1JMF, 1JMG, 1JMH, 1JMI, 1TVU, 1TVV, 1TVW 
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1997

A novel dCMP methylase by engineering thymidylate synthase.
Agarwalla, S; LaPorte, S; Liu, L; Finer-Moore, J; Stroud, RM; and Santi, DV. (1997)
Biochemistry 36, 15909-15917  
Review abstract
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Access to phosphorylation in isocitrate dehydrogenase may occur by domain shifting.
Finer-Moore, J; Tsutakawa, SE; Cherbavaz, DB; LaPorte, DC; Koshland, DE Jr; and Stroud, RM. (1997)
Biochemistry 36, 13890-13896
PDB Accession No. 1SJS
Review abstract
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A designed four helix bundle protein  with native-like structure.
Schafmeister CE; LaPorte SL; Miercke LJ; and Stroud RM. (1997)
Nature Structural Biology 4,1039-1046
PDB Accession No. 4HB1
Review abstract
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The discovery, characterization and crystallographically determined binding mode of an FMOC-containing inhibitor of HIV-1 protease.
Rutenber, EE; De Voss, JJ; Hoffman, L; Stroud, RM; Lee, KH; Alvarez, J; McPhee, F; Craik, C; and Ortiz de Montellano, PR. (1997)
Bioorganic and Medicinal Chemistry 5, 1311-1320.
Review abstract
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Crystal structure of colicin Ia.
Wiener, M; Freymann, D; Ghosh, P; Stroud, RM.(1997)
Nature 385, 461-464.
PDB Accession No. 1CII
Review abstract 
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Structure of the conserved GTPase domain of the signal recognition particle.
Freymann, DM; Keenan, RJ; Stroud, RM;
and Walter, P.  (1997)
Nature 385, 361-64
PDB Accession No 1FFH
Review abstract
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1996

Three-dimensional structures of HIV-I and SIV protease product complexes.
Rose, RB; Craik, CS; Douglas, NL; Stroud, RM. (1996)
Biochemistry 35, 12933-12944.
PDB Accession Nos.: 1YTG (HIV-1 protease
complexed with P-I-V-NH2); 1YTH (HIV-1 protease complexed with Ac-S-L-N-F); 1YTI (SIV protease complexed with F-L-E-K); 1YTJ (SIV protease complexed with F(NO2)-E-A-Nle-S).
View PDB structure 1YTG, 1YTH, 1YTI, 1YTJ
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A new class of HIV-1 protease inhibitor: the crystallographic structure, inhibition and chemical synthesis of an aminimide peptide isostere.
Rutenber, EE; McPhee, F; Kaplan, AP; Gallion, SL; Hogan, JC Jr;Craik, CS; and Stroud, RM. (1996)
Bioorganic and Medicinal Chemistry 4, 1545-1558.
PDB Accession No. 3AID
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An essential role for water in an enzyme reaction mechanism: The crystal structure of the thymidylate synthase mutant E58Q.
Sage, CR; Rutenber, EE; Stout, TJ; and Stroud, RM. (1996)
Biochemistry 35, 16270-16281.
PDB Accession Nos. 1KCE (WT-TS), 1ZPR [E60(58)Q]
View PDB structure 1KCE, 1ZPR
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Binding of the anticancer drug ZD1694 to E. coli thymidylate synthase: assessing specificity and affinity.
Rutenber, EE; and Stroud, RM. (1996)
Structure 4, 1317-1324.
PDB Accession No. 2KCE
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Balancing ATP in the cell.
Stroud, RM. (1996)
Nature Structural Biology 3, 567-569. 
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Asparagine 229 mutants of thymidylate synthase catalyze the methylation of 3-methyl-2'-deoxyuridine 5'-monophosphate.
Costi, PM; Liu, L; Finer-Moore, JS; Stroud, RM; and Santi, DV. (1996)
Biochemistry 35, 3944-3949.
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Partitioning roles of side chains in affinity, orientation, and catalysis with structures for mutant complexes: asparagine-229 in thymidylate synthase.
Finer-Moore, JS; Liu, L; Schafmeister, CE; Birdsall, DL; Mau, T;
Santi, DV; and Stroud, RM. (1996)
Biochemistry 35, 5125-5136.
PDB Accession Nos: 1NJA, 1NJB, 1NJC, 1NJD , 1NJE
View PDB structure 1NJA, 1NJB, 1NJC, 1NJD, 1NJE
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Contribution of a salt bridge to binding affinity and dUMP orientation to catalytic rate: mutation of a substrate-binding arginine in thymidylate synthase.
Finer-Moore, JS; Fauman, EB; Morse, RJ; Santi, DV; Stroud, RM. (1996)
Protein Engineering 9,  69-75.
PDB Accession Nos: 1TSV, 1TSW, 1TSX, 1TSY , 1TSZ
View PDB structure 1TSV, 1TSW, 1TSX, 1TSY, 1TSZ
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Entropy in bi-substrate enzymes - proposed role of an alternate site in chaperoning substrate into, and products out of, thymidylate synthase.
Birdsall, DL; Finer-Moore, J; and Stroud, RM. (1996)
Journal of Molecular Biology 255, 522-535.
PDB Accession Nos: 1VZA, 1VZB, 1VZC, 1VZD , 1VZE
View PDB structure 1VZA, 1VZB, 1VZC, 1VZD, 1VZE
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The complex of the anti-cancer therapeutic, BW1843U89, with thymidylate synthase at 2.0 Å resolution: Implications for a new mode of inhibition.
Stout, TJ; and Stroud, RM. (1996)
Structure 4, 67-77.
PDB Accession Number: 1SYN
Review abstract
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