3SBI

Crystal structure of human carbonic anhydrase isozyme II with 4-[(2-pyrimidinylsulfanyl)acetyl]benzenesulfonamide

Summary for 3SBI

• Entry DOI: 10.2210/pdb3sbi/pdb
• Related: 3S8X 3S9T 3SAP 3SAX 3SBH
• Descriptor: Carbonic anhydrase 2, ZINC ION, DIMETHYL SULFOXIDE, ... (6 entities in total)
• Functional Keywords: drug design, sulfonamide, metal-binding, lyase-lyase inhibitor complex, lyase/lyase inhibitor
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm : P00918
• Total number of polymer chains: 1
• Total formula weight: 29983.27

Authors

Grazulis, S.,Manakova, E.,Tamulaitiene, G. (deposition date: 2011-06-05, release date: 2012-04-11, Last modification date: 2023-09-13)

Primary citation

Capkauskaite, E.,Zubriene, A.,Baranauskiene, L.,Tamulaitiene, G.,Manakova, E.,Kairys, V.,Grazulis, S.,Tumkevicius, S.,Matulis, D.
Design of [(2-pyrimidinylthio)acetyl]benzenesulfonamides as inhibitors of human carbonic anhydrases.
Eur.J.Med.Chem., 51:259-270, 2012

PubMed Abstract: A series of [(2-pyrimidinylthio)acetyl]benzenesulfonamides were designed and synthesized. Their binding affinities as inhibitors of several recombinant human carbonic anhydrase (CA) isozymes were determined by isothermal titration calorimetry (ITC) and thermal shift assay (TSA). A group of compounds containing a chlorine atom in the benzenesulfonamide ring were found to exhibit higher selectivity but lower binding affinity toward tested CAs. The crystal structures of selected compounds in complex with CA II were determined to atomic resolution. Docking studies were performed to compare the binding modes of experimentally determined crystallographic structures with computational prediction of the pyrimidine derivative binding to CA II. Several compounds bound to select CAs with single-digit nanomolar affinities and could be used as leads for inhibitor development toward a select CA isozyme.

PubMed: 22440859
DOI: 10.1016/j.ejmech.2012.02.050

Experimental method

X-RAY DIFFRACTION (1.4 Å)