High-resolution structure of human carbonic anhydrase II complexed with acetazolamide reveals insights into inhibitor drug design. Acta crystallographica. Section F, Structural biology and crystallization communications [Acta Crystallogr Sect F Struct Biol Cryst Commun] Journal article | | Title | High-resolution structure of human carbonic anhydrase II complexed with acetazolamide reveals insights into inhibitor drug design. | | Author(s) | Sippel KH, Robbins AH, Domsic J, Genis C, Agbandje-McKenna M, McKenna R | | Institution | Department of Biochemistry and Molecular Biology, College of Medicine, University of Florida, Gainesville, FL 32610, USA. | | Source | Acta Crystallogr Sect F Struct Biol Cryst Commun 2009 Oct 1; 65(Pt 10):992-5. | | Abstract | The crystal structure of human carbonic anhydrase II (CA II) complexed with the inhibitor acetazolamide (AZM) has been determined at 1.1 A resolution and refined to an R(cryst) of 11.2% and an R(free) of 14.7%. As observed in previous CA II-inhibitor complexes, AZM binds directly to the zinc and makes several key interactions with active-site residues. The high-resolution data also showed a glycerol molecule adjacent to the AZM in the active site and two additional AZMs that are adventitiously bound on the surface of the enzyme. The co-binding of AZM and glycerol in the active site demonstrate that given an appropriate ring orientation and substituents, an isozyme-specific CA inhibitor may be developed. | | Language | eng | | Pub Type(s) | Journal Article
| | PubMed ID | 19851004 |
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