1j9w
From Proteopedia
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Solution Structure of the CAI Michigan 1 Variant
Overview
The human genetic variant carbonic anhydrase I (CA I) Michigan 1 results, from a single point mutation that changes His 67 to Arg in a critical, region of the active site. This variant of the zinc metalloenzyme appears, to be unique in that it possesses an esterase activity that is, specifically enhanced by added free zinc ions. We have determined the, three-dimensional structure of human CA I Michigan 1 by X-ray, crystallography to a resolution of 2.6 A. In the absence of added zinc, ions, the mutated residue, Arg 67, points out of the active site, hydrogen, bonding with the carboxylate of Asn 69. This contrasts with the, orientation of His 67, in the native isozyme, which points into the active, site. The orientations of His 94, His 96, and His 119, that coordinate the, catalytic zinc ion, and of the catalytically critical Thr 199-Glu 106, hydrogen bonding system, are largely unchanged in the mutant. The, structure of an enzyme adduct with a second zinc bound was determined to a, resolution of 2.0 A. The second zinc ion is coordinated to His 64, His, 200, and Arg 67. This arginine residue reverses its orientation on zinc, binding and turns into the active site. The residues at these three, positions have been implicated in determining the specific kinetic, properties of native CA I. This is, to our knowledge, the first example of, a zinc ion coordinating with an arginine residue in a Zn(II) enzyme.
About this Structure
1J9W is a Single protein structure of sequence from Homo sapiens with ZN and EDO as ligands. Active as Carbonate dehydratase, with EC number 4.2.1.1 Full crystallographic information is available from OCA.
Reference
Crystal structure of a zinc-activated variant of human carbonic anhydrase I, CA I Michigan 1: evidence for a second zinc binding site involving arginine coordination., Ferraroni M, Tilli S, Briganti F, Chegwidden WR, Supuran CT, Wiebauer KE, Tashian RE, Scozzafava A, Biochemistry. 2002 May 21;41(20):6237-44. PMID:12009884
Page seeded by OCA on Mon Nov 12 17:38:46 2007
