1bq1

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[[Image:1bq1.gif|left|200px]]
[[Image:1bq1.gif|left|200px]]
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{{Structure
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|PDB= 1bq1 |SIZE=350|CAPTION= <scene name='initialview01'>1bq1</scene>, resolution 2.5&Aring;
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The line below this paragraph, containing "STRUCTURE_1bq1", creates the "Structure Box" on the page.
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|SITE=
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You may change the PDB parameter (which sets the PDB file loaded into the applet)
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|LIGAND= <scene name='pdbligand=CB3:10-PROPARGYL-5,8-DIDEAZAFOLIC+ACID'>CB3</scene>, <scene name='pdbligand=CXM:N-CARBOXYMETHIONINE'>CXM</scene>, <scene name='pdbligand=UMP:2&#39;-DEOXYURIDINE+5&#39;-MONOPHOSPHATE'>UMP</scene>
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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|ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/Thymidylate_synthase Thymidylate synthase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.1.1.45 2.1.1.45] </span>
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or leave the SCENE parameter empty for the default display.
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|GENE= THYA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=562 Escherichia coli])
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|DOMAIN=
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{{STRUCTURE_1bq1| PDB=1bq1 | SCENE= }}
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|RELATEDENTRY=
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|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1bq1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1bq1 OCA], [http://www.ebi.ac.uk/pdbsum/1bq1 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1bq1 RCSB]</span>
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'''E. COLI THYMIDYLATE SYNTHASE MUTANT N177A IN COMPLEX WITH CB3717 AND 2'-DEOXYURIDINE 5'-MONOPHOSPHATE (DUMP)'''
'''E. COLI THYMIDYLATE SYNTHASE MUTANT N177A IN COMPLEX WITH CB3717 AND 2'-DEOXYURIDINE 5'-MONOPHOSPHATE (DUMP)'''
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[[Category: Sage, C R.]]
[[Category: Sage, C R.]]
[[Category: Stroud, R M.]]
[[Category: Stroud, R M.]]
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[[Category: active site mutant]]
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[[Category: Active site mutant]]
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[[Category: reaction intermediate]]
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[[Category: Reaction intermediate]]
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[[Category: transferase]]
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[[Category: Transferase]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 11:48:55 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 19:05:53 2008''
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Revision as of 08:48, 2 May 2008

Template:STRUCTURE 1bq1

E. COLI THYMIDYLATE SYNTHASE MUTANT N177A IN COMPLEX WITH CB3717 AND 2'-DEOXYURIDINE 5'-MONOPHOSPHATE (DUMP)


Overview

Mutation of thymidylate synthase N229(177) to alanine results in an essentially inactive enzyme, yet it leads to formation of a stable ternary complex. The kinetics of N229(177)A show that kcat for Escherichia coli is reduced by 200-fold while the Km for dUMP is increased 200-fold and the Km for folate increased by tenfold versus the wild-type enzyme. The crystal structures of N229(177)A in complex with dUMP and CB3717, and in complex with dUMP alone are determined at 2.4 A, and 2.5 A resolution. These structures identify the covalently bound ternary complex and show how N229(177)A traps an intermediate, and so becomes inactive in a later step of the reaction. Since the smaller alanine side-chain at N229(177)A does not directly sterically impair binding of ligands, the structures implicate, and place quantitative limits on the involvement of the structured water network in the active site of thymidylate synthase in both catalysis and in determining the binding affinity for dUMP (in contrast, the N229(177)V mutation in Lactobacillus casei has minimal effect on activity).

About this Structure

1BQ1 is a Single protein structure of sequence from Escherichia coli. Full crystallographic information is available from OCA.

Reference

Inactivity of N229A thymidylate synthase due to water-mediated effects: isolating a late stage in methyl transfer., Reyes CL, Sage CR, Rutenber EE, Nissen RM, Finer-Moore JS, Stroud RM, J Mol Biol. 1998 Dec 4;284(3):699-712. PMID:9826509 Page seeded by OCA on Fri May 2 11:48:55 2008

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