Sippel KH, Robbins AH, Domsic J, Genis C, Agbandje-McKenna M, McKenna R
High-resolution structure of human carbonic anhydrase II complexed with acetazolamide reveals insights into inhibitor drug design. [Journal Article]
Acta Crystallogr Sect F Struct Biol Cryst Commun 2009 Oct 1; 65(Pt 10):992-5.
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.
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