1eb3: Difference between revisions
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==Overview== | ==Overview== | ||
The structures of 5-aminolaevulinic acid dehydratase complexed with two | 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== | ==About this Structure== | ||
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[[Category: Saccharomyces cerevisiae]] | [[Category: Saccharomyces cerevisiae]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Brindley, A | [[Category: Brindley, A A.]] | ||
[[Category: Coates, L.]] | [[Category: Coates, L.]] | ||
[[Category: Cooper, J | [[Category: Cooper, J B.]] | ||
[[Category: Erskine, P | [[Category: Erskine, P T.]] | ||
[[Category: Neier, R.]] | [[Category: Neier, R.]] | ||
[[Category: Newbold, R.]] | [[Category: Newbold, R.]] | ||
[[Category: Shoolingin-Jordan, P | [[Category: Shoolingin-Jordan, P M.]] | ||
[[Category: Stauffer, F.]] | [[Category: Stauffer, F.]] | ||
[[Category: Warren, M | [[Category: Warren, M J.]] | ||
[[Category: Wood, S | [[Category: Wood, S P.]] | ||
[[Category: DSB]] | [[Category: DSB]] | ||
[[Category: ZN]] | [[Category: ZN]] | ||
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[[Category: tim barrel]] | [[Category: tim barrel]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:25:51 2008'' | ||
Revision as of 10:25, 21 February 2008
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YEAST 5-AMINOLAEVULINIC ACID DEHYDRATASE 4,7-DIOXOSEBACIC ACID COMPLEX
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
1EB3 is a Single protein structure of sequence from Saccharomyces cerevisiae with ZN and DSB as ligands. Active as Porphobilinogen synthase, with EC number 4.2.1.24 Known structural/functional Sites: AC1 and AC2. 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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