1okl

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

CARBONIC ANHYDRASE II COMPLEX WITH THE 1OKL INHIBITOR 5-DIMETHYLAMINO-NAPHTHALENE-1-SULFONAMIDE

Contents 1 Overview 2 Disease 3 About this Structure 4 Reference

Overview

The three-dimensional structure of human carbonic anhydrase II (CAII), complexed with the sulfonamide fluorophore 5-dimethylamino-1-naphthalene, sulfonamide (dansylamide) has been determined to 2.1-A resolution by x-ray, crystallographic methods. Unlike other arylsulfonamide inhibitors of CAII, the naphthyl ring of dansylamide binds in a hydrophobic pocket in the, active site, making van der Waals contacts with Val-121, Phe-131, Val-143, Leu-198, and Trp-209. Interestingly, a conformational change of Leu-198 is, required to accommodate dansylamide binding, which rationalizes the, enhanced dansylamide affinity measured for certain Leu-198 variants (Nair, S. K., Krebs, J.F., Christianson, D. W., and Fierke, C. A. (1995), Biochemistry 34, 3981-3989). Modeling studies indicate that a second, binding mode, in which the fused aromatic ring is rotated out of the, hydrophobic pocket, is sterically feasible. Both experimentally observed, and modeled binding modes have implications for new leads in the design of, avid CAII inhibitors. Finally, the structure of the CAII-dansylamide, complex has implications for its exploitation in zinc biosensor, applications, and possible routes toward the optimization of fluorophore, design are considered on the basis on this structure.

Disease

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

About this Structure

1OKL is a Single protein structure of sequence from Homo sapiens with HG, ZN and MNS as ligands. Active as Carbonate dehydratase, with EC number 4.2.1.1 Full crystallographic information is available from OCA.

Reference

Unexpected binding mode of the sulfonamide fluorophore 5-dimethylamino-1-naphthalene sulfonamide to human carbonic anhydrase II. Implications for the development of a zinc biosensor., Nair SK, Elbaum D, Christianson DW, J Biol Chem. 1996 Jan 12;271(2):1003-7. PMID:8557623

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