8acn
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(New page: 200px<br /><applet load="8acn" size="450" color="white" frame="true" align="right" spinBox="true" caption="8acn, resolution 2.0Å" /> '''CRYSTAL STRUCTURES OF...)
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Revision as of 13:02, 20 November 2007
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CRYSTAL STRUCTURES OF ACONITASE WITH ISOCITRATE AND NITROISOCITRATE BOUND
Overview
The crystal structures of mitochondrial aconitase with isocitrate and, nitroisocitrate bound have been solved and refined to R factors of 0.179, and 0.161, respectively, for all observed data in the range 8.0-2.1 A., Porcine heart enzyme was used for determining the structure with, isocitrate bound. The presence of isocitrate in the crystals was, corroborated by Mossbauer spectroscopy. Bovine heart enzyme was used for, determining the structure with the reaction intermediate analogue, nitroisocitrate bound. The inhibitor binds to the enzyme in a manner, virtually identical to that of isocitrate. Both compounds bind to the, unique Fe atom of the [4Fe-4S] cluster via a hydroxyl oxygen and one, carboxyl oxygen. A H2O molecule is also bound, making Fe six-coordinate., The unique Fe is pulled away approximately 0.2 A from the corner of the, cubane compared to the position it would occupy in a symmetrically ligated, [4Fe-4S] cluster. At least 23 residues from all four domains of aconitase, contribute to the active site. These residues participate in substrate, recognition (Arg447, Arg452, Arg580, Arg644, Gln72, Ser166, Ser643), cluster ligation and interaction (Cys358, Cys421, Cys424, Asn258, Asn446), and hydrogen bonds supporting active site side chains (Ala74, Asp568, Ser571, Thr567). Residues implicated in catalysis are Ser642 and three, histidine-carboxylate pairs (Asp100-His101, Asp165-His147, Glu262-His167)., The base necessary for proton abstraction from C beta of isocitrate, appears to be Ser642; the O gamma atom is proximal to the calculated, hydrogen position, while the environment of O gamma suggests stabilization, of an alkoxide (an oxyanion hole formed by the amide and side chain of, Arg644). The histidine-carboxylate pairs appear to be required for proton, transfer reactions involving two oxygens bound to Fe, one derived from, solvent (bound H2O) and one derived from substrate hydroxyl. Each oxygen, is in contact with a histidine, and both are in contact with the side, chain of Asp165, which bridges the two sites on the six-coordinate Fe.
About this Structure
8ACN is a Single protein structure of sequence from Bos taurus with SF4 and NIC as ligands. Active as Aconitate hydratase, with EC number 4.2.1.3 Full crystallographic information is available from OCA.
Reference
Crystal structures of aconitase with isocitrate and nitroisocitrate bound., Lauble H, Kennedy MC, Beinert H, Stout CD, Biochemistry. 1992 Mar 17;31(10):2735-48. PMID:1547214
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