1gjp

From Proteopedia

Revision as of 14:08, 5 November 2007

SCHIFF-BASE COMPLEX OF YEAST 5-AMINOLAEVULINIC ACID DEHYDRATASE WITH 4-OXOSEBACIC ACID

Overview

The structures of 5-aminolaevulinic acid dehydratase complexed with two, irreversible inhibitors (4-oxosebacic acid and 4,7-dioxosebacic acid) have, been solved at high resolution. Both inhibitors bind by forming a Schiff, base link with Lys 263 at the active site. Previous inhibitor binding, studies have defined the interactions made by only one of the two, substrate moieties (P-side substrate) which bind to the enzyme during, catalysis. The structures reported here provide an improved definition of, the interactions made by both of the substrate molecules (A- and P-side, substrates). The most intriguing result is the novel finding that, 4,7-dioxosebacic acid forms a second Schiff base with the enzyme involving, Lys 210. It has been known for many years that P-side substrate forms a, Schiff base (with Lys 263) but until now there has been no evidence that, binding of A-side substrate involves formation of a Schiff base with the, enzyme. A catalytic mechanism involving substrate linked to the enzyme, through Schiff bases at both the A- and P-sites is proposed.

About this Structure

1GJP is a Single protein structure of sequence from Saccharomyces cerevisiae with ZN and 4OX as ligands. Active as Porphobilinogen synthase, with EC number 4.2.1.24 Structure known Active Site: AC1. Full crystallographic information is available from OCA.

Reference

The X-ray structure of yeast 5-aminolaevulinic acid dehydratase complexed with two diacid inhibitors., Erskine PT, Coates L, Newbold R, Brindley AA, Stauffer F, Wood SP, Warren MJ, Cooper JB, Shoolingin-Jordan PM, Neier R, FEBS Lett. 2001 Aug 17;503(2-3):196-200. PMID:11513881

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