1tys

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{{STRUCTURE_1tys| PDB=1tys | SCENE= }}
{{STRUCTURE_1tys| PDB=1tys | SCENE= }}
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'''WATER-MEDIATED SUBSTRATE(SLASH)PRODUCT DISCRIMINATION: THE PRODUCT COMPLEX OF THYMIDYLATE SYNTHASE AT 1.83 ANGSTROMS'''
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===WATER-MEDIATED SUBSTRATE(SLASH)PRODUCT DISCRIMINATION: THE PRODUCT COMPLEX OF THYMIDYLATE SYNTHASE AT 1.83 ANGSTROMS===
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==Overview==
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In an irreversible enzyme-catalyzed reaction, strong binding of the products would lead to substantial product inhibition. The X-ray crystal structure of the product complex of thymidylate synthase (1.83-A resolution, R factor = 0.183 for all data between 7.0 and 1.83 A) identifies a bound water molecule that serves to disfavor binding of the product nucleotide, dTMP. This water molecule is hydrogen bonded to absolutely conserved Tyr 146 (using the Lactobacillus casei numbering system) and is displaced by the C7 methyl group of the reaction product thymidylate. The relation between this observation and kinetic and thermodynamic values is discussed. The structure reveals a carbamate modified N-terminus that binds in a highly conserved site, replaced by side chains that can exploit the same site in other TS sequences. The enzyme-products complex is compared to the previously determined structure of enzyme-substrate-cofactor analog. This comparison reveals changes that occur between the first covalent complex formed between enzyme and substrate with an inhibitory cofactor analog and the completed reaction. The almost identical arrangement of ligands in these two structures contributes to our model for the TS reaction and verifies the physiological relevance of the mode in which potent inhibitors bind to this target for rational drug design.
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(as it appears on PubMed at http://www.pubmed.gov), where 8312270 is the PubMed ID number.
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{{ABSTRACT_PUBMED_8312270}}
==About this Structure==
==About this Structure==
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[[Category: Rutenber, E.]]
[[Category: Rutenber, E.]]
[[Category: Stroud, R.]]
[[Category: Stroud, R.]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 00:44:06 2008''

Revision as of 21:44, 27 July 2008

Image:1tys.png

Template:STRUCTURE 1tys

WATER-MEDIATED SUBSTRATE(SLASH)PRODUCT DISCRIMINATION: THE PRODUCT COMPLEX OF THYMIDYLATE SYNTHASE AT 1.83 ANGSTROMS

Template:ABSTRACT PUBMED 8312270

About this Structure

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

Reference

Water-mediated substrate/product discrimination: the product complex of thymidylate synthase at 1.83 A., Fauman EB, Rutenber EE, Maley GF, Maley F, Stroud RM, Biochemistry. 1994 Feb 15;33(6):1502-11. PMID:8312270

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