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6G7A

Crystal structure of human carbonic anhydrase isozyme XII 2-(benzylamino)-4-chloro-N-(2-hydroxyethyl)-5-sulfamoyl-benzamide

Summary for 6G7A
Entry DOI10.2210/pdb6g7a/pdb
Related6G5L 6G5U 6G6T
DescriptorCarbonic anhydrase 12, ZINC ION, 1,2-ETHANEDIOL, ... (5 entities in total)
Functional Keywordsdrug design, carbonic anhydrase, benzenesulfonamide, metal-binding, lyase-lyase inhibitor comple, lyase
Biological sourceHomo sapiens (Human)
Total number of polymer chains4
Total formula weight122211.12
Authors
Smirnov, A.,Manakova, E.,Grazulis, S. (deposition date: 2018-04-05, release date: 2019-03-13, Last modification date: 2024-11-06)
Primary citationZaksauskas, A.,Capkauskaite, E.,Jezepcikas, L.,Linkuviene, V.,Kisonaite, M.,Smirnov, A.,Manakova, E.,Grazulis, S.,Matulis, D.
Design of two-tail compounds with rotationally fixed benzenesulfonamide ring as inhibitors of carbonic anhydrases.
Eur J Med Chem, 156:61-78, 2018
Cited by
PubMed Abstract: Rational design of compounds that would bind specific pockets of the target proteins is a difficult task in drug design. The 12 isoforms of catalytically active human carbonic anhydrases (CAs) have highly similar active sites that make it difficult to design inhibitors selective for one or several CA isoforms. A series of CA inhibitors based on 2-chloro/bromo-benzenesulfonamide that is largely fixed in the CA active site together with one or two tails yielded compounds that were synthesized and evaluated as inhibitors of CA isoforms. Introduction of a second tail had significant influence on the binding affinity and two-tailed compounds in most cases provided high affinity and selectivity for CA IX and CA XIV. The contacts between several compounds and CA amino acids were determined by X-ray crystallography. Together with the intrinsic enthalpy and entropy of binding they provided the structure-thermodynamics correlations for this series of compounds with the insight how to rationally build compounds with desired CA isoform as a target.
PubMed: 30006175
DOI: 10.1016/j.ejmech.2018.06.059
PDB entries with the same primary citation
Experimental method
X-RAY DIFFRACTION (1.42 Å)
Structure validation

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数据于2025-10-15公开中

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