2FOQ

Human Carbonic Anhydrase II complexed with two-prong inhibitors

Summary for 2FOQ

• Entry DOI: 10.2210/pdb2foq/pdb
• Related: 2CBA
• Descriptor: Carbonic anhydrase 2, ZINC ION, [2,2'-({4-[({2-[4-(AMINOSULFONYL)PHENYL]ETHYL}AMINO)CARBONYL]BENZYL}IMINO)DIACETATO(2-)-KAPPAO]COPPER, ... (5 entities in total)
• Functional Keywords: lyase, inhibitor
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 1
• Total formula weight: 30683.19

Authors

Jude, K.M.,Christianson, D.W. (deposition date: 2006-01-13, release date: 2006-02-28, Last modification date: 2024-10-09)

Primary citation

Jude, K.M.,Banerjee, A.L.,Haldar, M.K.,Manokaran, S.,Roy, B.,Mallik, S.,Srivastava, D.K.,Christianson, D.W.
Ultrahigh resolution crystal structures of human carbonic anhydrases I and II complexed with two-prong inhibitors reveal the molecular basis of high affinity.
J.Am.Chem.Soc., 128:3011-3018, 2006

PubMed Abstract: The atomic-resolution crystal structures of human carbonic anhydrases I and II complexed with "two-prong" inhibitors are reported. Each inhibitor contains a benzenesulfonamide prong and a cupric iminodiacetate (IDA-Cu(2+)) prong separated by linkers of different lengths and compositions. The ionized NH(-) group of each benzenesulfonamide coordinates to the active site Zn(2+) ion; the IDA-Cu(2+) prong of the tightest-binding inhibitor, BR30, binds to H64 of CAII and H200 of CAI. This work provides the first evidence verifying the structural basis of nanomolar affinity measured for two-prong inhibitors targeting the carbonic anhydrases.

PubMed: 16506782
DOI: 10.1021/ja057257n

Experimental method

X-RAY DIFFRACTION (1.25 Å)