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(9): 3011-8, 2006 Mar 08.
Article
in En
| MEDLINE
| ID: mdl-16506782
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Carbonic Anhydrase Inhibitors
/
Carbonic Anhydrase I
/
Carbonic Anhydrase II
Limits:
Humans
Language:
En
Journal:
J Am Chem Soc
Year:
2006
Document type:
Article
Affiliation country:
United States