1c3e: Difference between revisions

Revision as of 20:09, 30 June 2008

This article has been automatically seeded. Changes to this page should pertain to the PDB entry only and not to the protein or biomolecule in general.

File:1c3e.png

Template:STRUCTURE 1c3e

NEW INSIGHTS INTO INHIBITOR DESIGN FROM THE CRYSTAL STRUCTURE AND NMR STUDIES OF E. COLI GAR TRANSFORMYLATE IN COMPLEX WITH BETA-GAR AND 10-FORMYL-5,8,10-TRIDEAZAFOLIC ACID.NEW INSIGHTS INTO INHIBITOR DESIGN FROM THE CRYSTAL STRUCTURE AND NMR STUDIES OF E. COLI GAR TRANSFORMYLATE IN COMPLEX WITH BETA-GAR AND 10-FORMYL-5,8,10-TRIDEAZAFOLIC ACID.

Template:ABSTRACT PUBMED 10606510

About this StructureAbout this Structure

1C3E is a Single protein structure of sequence from Escherichia coli. Full crystallographic information is available from OCA.

ReferenceReference

New insights into inhibitor design from the crystal structure and NMR studies of Escherichia coli GAR transformylase in complex with beta-GAR and 10-formyl-5,8,10-trideazafolic acid., Greasley SE, Yamashita MM, Cai H, Benkovic SJ, Boger DL, Wilson IA, Biochemistry. 1999 Dec 21;38(51):16783-93. PMID:10606510

Page seeded by OCA on Mon Jun 30 20:09:10 2008

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OCA

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 {{STRUCTURE_1c3e|  PDB=1c3e  |  SCENE=  }}
-'''NEW INSIGHTS INTO INHIBITOR DESIGN FROM THE CRYSTAL STRUCTURE AND NMR STUDIES OF E. COLI GAR TRANSFORMYLATE IN COMPLEX WITH BETA-GAR AND 10-FORMYL-5,8,10-TRIDEAZAFOLIC ACID.'''
+===NEW INSIGHTS INTO INHIBITOR DESIGN FROM THE CRYSTAL STRUCTURE AND NMR STUDIES OF E. COLI GAR TRANSFORMYLATE IN COMPLEX WITH BETA-GAR AND 10-FORMYL-5,8,10-TRIDEAZAFOLIC ACID.===
-==Overview==
+<!--
-The crystal structure of Escherichia coli GAR Tfase at 2.1 A resolution in complex with 10-formyl-5,8,10-trideazafolic acid (10-formyl-TDAF, K(i) = 260 nM), an inhibitor designed to form an enzyme-assembled multisubstrate adduct with the substrate, beta-GAR, was studied to determine the exact nature of its inhibitory properties. Rather than forming the expected covalent adduct, the folate inhibitor binds as the hydrated aldehyde (gem-diol) in the enzyme active site, in a manner that mimics the tetrahedral intermediate of the formyl transfer reaction. In this hydrated form, the inhibitor not only provides unexpected insights into the catalytic mechanism but also explains the 10-fold difference in inhibitor potency between 10-formyl-TDAF and the corresponding alcohol, and a further 10-fold difference for inhibitors that lack the alcohol. The presence of the hydrated aldehyde was confirmed in solution by (13)C-(1)H NMR spectroscopy of the ternary GAR Tfase-beta-GAR-10-formyl-TDAF complex using the (13)C-labeled 10-formyl-TDAF. This insight into the behavior of the inhibitor, which is analogous to protease or transaminase inhibitors, provides a novel and previously unrecognized basis for the design of more potent inhibitors of the folate-dependent formyl transfer enzymes of the purine biosynthetic pathway and development of anti-neoplastic agents.
+The line below this paragraph, {{ABSTRACT_PUBMED_10606510}}, adds the Publication Abstract to the page
+(as it appears on PubMed at http://www.pubmed.gov), where 10606510 is the PubMed ID number.
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+{{ABSTRACT_PUBMED_10606510}}
 ==About this Structure==
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 [[Category: Inhibitor complex]]
 [[Category: Purine biosynthesis]]
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