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Theoretical improvement of the specific inhibitor of human carbonic anhydrase VII

Paper ID Volume ID Publish Year Pages File Format Full-Text
15266 1398 2011 7 PDF Available
Title
Theoretical improvement of the specific inhibitor of human carbonic anhydrase VII
Abstract

The selectivity of a known arylsulfonamides inhibitor for two isozymes II and VII of human carbonic anhydrases (hCAs) was studied by homology modeling, molecular docking and molecular dynamics methods. The results show that the selectivity of the inhibitor for two isozymes is due to the different side chain lengths between N67 of hCA II and Q64 of hCA VII. One more methene group in the side chain of Q64 of hCA VII makes it possible to form the hydrogen bond with the bromide atom of the known inhibitor. From the point of view, the modification to the known inhibitor was performed to obtain an inhibitor with higher selectivity. The complex conformations of the new designed inhibitor and two isozymes designate the formation of the hydrogen bond between the newly added group (hydroxypropyl group) and Q64 of hCA VII but N67 of hCA II. The results of the binding free energy from the MM/PBSA approach also prove the selectivity improvement of the new inhibitor in comparison with the known inhibitor. The work will help the design of the isozyme-specific inhibitors of hCA VII.

Graphical abstractFigure optionsDownload full-size imageDownload as PowerPoint slideResearch highlights► The selective mechanism of a known inhibitor for two isozymes (II and VII) of human carbonic anhydrase (hCA) was investigated by homology modeling, molecular docking and molecular dynamics methods. ► On the basis of the obtained results, the modification to the known inhibitor was performed to design a new hCA VII-specific inhibitor. ► The new inhibitor strengthens the interaction with hCA VII by a newly added group and increases the selectivity for hCA VII.

Keywords
Human carbonic anhydrase; Isozyme-specific inhibitor; Arylsulfonamides; Homology modeling; Molecular docking
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Theoretical improvement of the specific inhibitor of human carbonic anhydrase VII
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Publisher
Database: Elsevier - ScienceDirect
Journal: Computational Biology and Chemistry - Volume 35, Issue 1, February 2011, Pages 50–56
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us