This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.
Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.
2qp6
From Proteopedia
The crystal structure of the complex of hcaII with a bioreductive antitumor derivative
Overview
2-Substituted-5-nitro-benzenesulfonamides incorporating a large variety of secondary/tertiary amines were explored as inhibitors of the zinc enzyme carbonic anhydrase (CA, EC 4.2.1.1), with the aim of designing bioreductive inhibitors targeting the hypoxia overexpressed, tumor-associated isozymes. The compounds were ineffective inhibitors of the cytosolic isoform I, showed a better inhibition of the physiologically relevant CA II ( K Is of 8.8-4975 nM), and strongly inhibited the tumor-associated CA IX and XII ( K Is of 5.4-653 nM). Some of these compounds showed excellent selectivity ratios for the inhibition of the tumor-associated isozymes over the cytosolic ones (in the range of 10-1395). The X-ray crystal structure of the adduct of hCA II with the lead molecule 2-chloro-5-nitro-benzenesulfonamide as well as molecular modeling studies for interaction with hCA IX afforded a better understanding of factors governing the discrimination of the two isoforms for this type of bioreductive compound targeting specifically hypoxic tumors.
About this Structure
2QP6 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Carbonic Anhydrase Inhibitors: Bioreductive Nitro-Containing Sulfonamides with Selectivity for Targeting the Tumor Associated Isoforms IX and XII., D'Ambrosio K, Vitale RM, Dogne JM, Masereel B, Innocenti A, Scozzafava A, De Simone G, Supuran CT, J Med Chem. 2008 May 16;. PMID:18481843 Page seeded by OCA on Wed Jun 4 09:52:02 2008
