1dcb

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spinqualitylabelsall models 1dcb, resolution 2.1Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

STRUCTURE OF AN ENGINEERED METAL BINDING SITE IN HUMAN CARBONIC ANHYDRASE II REVEALS THE ARCHITECTURE OF A REGULATORY CYSTEINE SWITCH

Contents 1 Overview 2 Disease 3 About this Structure 4 Reference

Overview

X-ray crystallographic analysis of the Thr-199-->Cys (T199C) variant of, human carbonic anhydrase II reveals the first high-resolution structure of, an engineered zinc coordination polyhedron in a metalloenzyme. In the, wild-type enzyme, Thr-199 accepts a hydrogen bond from zinc-bound, hydroxide; in the variant, the polypeptide backbone is sufficiently, plastic to permit Cys-199 to displace hydroxide ion and coordinate to zinc, with nearly perfect coordination stereochemistry. Importantly, the, resulting His3-Cys-Zn2+ motif binds zinc more tightly than the wild-type, enzyme [Kiefer, L. L., Krebs, J. F., Paterno, S. A., & Fierke C. A. (1993), Biochemistry (preceding paper in this issue)]. This novel zinc, coordination polyhedron is analogous to that postulated for matrix, metalloproteinase zymogens such as prostromelysin, where a cysteine-zinc, interaction is responsible for the inactivity of the zymogen., Intriguingly, Cys-199 of T199C CAII is displaced from zinc coordination by, soaking crystals in high concentrations of acetazolamide. Hence, residual, catalytic activity measured for this variant probably arises from an, alternate conformer of Cys-199 which allows the catalytic nucleophile, hydroxide ion, to be activated by zinc coordination.

Disease

Known disease associated with this structure: Osteopetrosis, autosomal recessive 3, with renal tubular acidosis OMIM:[611492]

About this Structure

1DCB is a Single protein structure of sequence from Homo sapiens with ZN as ligand. Active as Carbonate dehydratase, with EC number 4.2.1.1 Full crystallographic information is available from OCA.

Reference

Structure of an engineered His3Cys zinc binding site in human carbonic anhydrase II., Ippolito JA, Christianson DW, Biochemistry. 1993 Sep 28;32(38):9901-5. PMID:8399159

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