1xg4
From Proteopedia
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Crystal Structure of the C123S 2-Methylisocitrate Lyase Mutant from Escherichia coli in complex with the inhibitor isocitrate
Overview
Two crystal structures of the C123S mutant of 2-methylisocitrate lyase, have been determined, one with the bound reaction products, Mg(2+)-pyruvate and succinate, and the second with a bound, Mg(2+)-(2R,3S)-isocitrate inhibitor. Comparison with the structure of the, wild-type enzyme in the unbound state reveals that the enzyme undergoes a, conformational transition that sequesters the ligand from solvent, as, previously observed for two other enzyme superfamily members, isocitrate, lyase and phosphoenolpyruvate mutase. The binding modes reveal the, determinants of substrate specificity and stereoselectivity, and the, stringent specificity is verified in solution using various potential, substrates. A model of bound 2-methylisocitrate has been developed based, on the experimentally determined structures. We propose a catalytic, mechanism involving an alpha-carboxy-carbanion intermediate/transition, state, which is consistent with previous stereochemical experiments, showing inversion of configuration at the C(3) of 2-methylisocitrate., Structure-based sequence analysis and phylogenic tree construction reveal, determinants of substrate specificity, highlight nodes of divergence of, families, and predict enzyme families with new functions.
About this Structure
1XG4 is a Single protein structure of sequence from Escherichia coli with MG and ICT as ligands. Active as Methylisocitrate lyase, with EC number 4.1.3.30 Full crystallographic information is available from OCA.
Reference
Crystal structures of 2-methylisocitrate lyase in complex with product and with isocitrate inhibitor provide insight into lyase substrate specificity, catalysis and evolution., Liu S, Lu Z, Han Y, Melamud E, Dunaway-Mariano D, Herzberg O, Biochemistry. 2005 Mar 1;44(8):2949-62. PMID:15723538
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