2FOY

Human Carbonic Anhydrase I complexed with a two-prong inhibitor

Summary for 2FOY

• Entry DOI: 10.2210/pdb2foy/pdb
• Related: 1HCB 2FOQ 2FOS 2FOU 2FOV
• Descriptor: Carbonic anhydrase 1, ZINC ION, {2,2'-[(2-{[4-(AMINOSULFONYL)BENZOYL]AMINO}ETHYL)IMINO]DIACETATO(2-)-KAPPAO}COPPER, ... (4 entities in total)
• Functional Keywords: lyase, zinc, inhibitor, copper
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm: P00915
• Total number of polymer chains: 2
• Total formula weight: 60206.10

Authors

Jude, K.M.,Banerjee, A.L.,Haldar, M.K.,Manokaran, S.,Roy, B.,Mallik, S.,Srivastava, D.K.,Christianson, D.W. (deposition date: 2006-01-14, release date: 2006-04-04, Last modification date: 2023-08-30)

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 (1.55 Å)