1OKL

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

1OKL の概要

• エントリーDOI: 10.2210/pdb1okl/pdb
• 分子名称: CARBONIC ANHYDRASE II, MERCURY (II) ION, ZINC ION, ... (5 entities in total)
• 機能のキーワード: lyase (oxo-acid), inhibitor, lyase
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cytoplasm: P00918
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 29674.18

構造登録者

Nair, S.K.,Elbaum, D.,Christianson, D.W. (登録日: 1996-06-25, 公開日: 1997-01-11, 最終更新日: 2024-02-14)

主引用文献

Nair, S.K.,Elbaum, D.,Christianson, D.W.
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.
J.Biol.Chem., 271:1003-1007, 1996

PubMed Abstract: 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.

PubMed: 8557623

実験手法

X-RAY DIFFRACTION (2.1 Å)