1bnt: Difference between revisions

Revision as of 11:44, 2 May 2008

CARBONIC ANHYDRASE II INHIBITOR

OverviewOverview

X-ray crystal structures of carbonic anhydrase II (CAII) complexed with sulfonamide inhibitors illuminate the structural determinants of high affinity binding in the nanomolar regime. The primary binding interaction is the coordination of a primary sulfonamide group to the active site zinc ion. Secondary interactions fine-tune tight binding in regions of the active site cavity >5 A away from zinc, and this work highlights three such features: (1) advantageous conformational restraints of a bicyclic thienothiazene-6-sulfonamide-1,1-dioxide inhibitor skeleton in comparison with a monocyclic 2,5-thiophenedisulfonamide skeleton; (2) optimal substituents attached to a secondary sulfonamide group targeted to interact with hydrophobic patches defined by Phe131, Leu198, and Pro202; and (3) optimal stereochemistry and configuration at the C-4 position of bicyclic thienothiazene-6-sulfonamides; the C-4 substituent can interact with His64, the catalytic proton shuttle. Structure-activity relationships rationalize affinity trends observed during the development of brinzolamide (Azopt), the newest carbonic anhydrase inhibitor approved for the treatment of glaucoma.

About this StructureAbout this Structure

1BNT is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

ReferenceReference

Structural analysis of inhibitor binding to human carbonic anhydrase II., Boriack-Sjodin PA, Zeitlin S, Chen HH, Crenshaw L, Gross S, Dantanarayana A, Delgado P, May JA, Dean T, Christianson DW, Protein Sci. 1998 Dec;7(12):2483-9. PMID:9865942 Page seeded by OCA on Fri May 2 11:44:49 2008

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

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 [[Image:1bnt.gif|left|200px]]
- {{Structure
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-}}
 '''CARBONIC ANHYDRASE II INHIBITOR'''
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 [[Category: Christianson, D W.]]
 [[Category: Zeitlin, S.]]
-[[Category: co2 hydration]]
+[[Category: Co2 hydration]]
-[[Category: lyase]]
+[[Category: Lyase]]
-[[Category: zinc enzyme]]
+[[Category: Zinc enzyme]]
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May  2 11:44:49 2008''
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 19:04:42 2008''