1ci7
From Proteopedia
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TERNARY COMPLEX OF THYMIDYLATE SYNTHASE FROM PNEUMOCYSTIS CARINII
Overview
Thymidylate synthase (TS), a half-the-sites reactive enzyme, catalyzes the, final step in the de novo biosynthesis of deoxythymidine monophosphate, dTMP, required for DNA replication. The cocrystal structure of TS from, Pneumocystis carinii (PcTS), a new drug target for an important pathogen, with its substrate, deoxyuridine monophosphate (dUMP), and a cofactor, mimic, CB3717, was determined. The structure, solved at 2.6 A resolution, shows an asymmetric dimer with two molecules of the substrate dUMP bound, yet only one molecule of cofactor analogue bound. The structural evidence, reveals that upon binding cofactor analogue and forming a covalent bond, from the nucleophilic cysteine to the substrate, dUMP, at one active site, PcTS undergoes a conformational change that renders the opposite monomer, incapable of forming a covalent bond or binding a molecule of cofactor, analogue. The communication pathway between the two active sites is, evident, allowing a structural definition of the basis of half-the-sites, reactivity for thymidylate synthase and providing an example of such a, mechanism for other half-the-sites reactive enzymes.
About this Structure
1CI7 is a Single protein structure of sequence from Pneumocystis carinii with UMP and CB3 as ligands. Active as Thymidylate synthase, with EC number 2.1.1.45 Full crystallographic information is available from OCA.
Reference
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, Stroud RM, Biochemistry. 1999 Oct 19;38(42):13829-36. PMID:10529228
Page seeded by OCA on Tue Nov 20 12:28:45 2007
