PMID- 9865942
OWN - NLM
STAT- MEDLINE
DCOM- 19990303
LR  - 20181113
IS  - 0961-8368 (Print)
IS  - 1469-896X (Electronic)
IS  - 0961-8368 (Linking)
VI  - 7
IP  - 12
DP  - 1998 Dec
TI  - Structural analysis of inhibitor binding to human carbonic anhydrase II.
PG  - 2483-9
AB  - X-ray crystal structures of carbonic anhydrase II (CAII) complexed with 
      sulfonamide inhibitors illuminate the structural determinants of high affinity 
      binding in the nanomolar regime. The primary binding interaction is the 
      coordination of a primary sulfonamide group to the active site zinc ion. 
      Secondary interactions fine-tune tight binding in regions of the active site 
      cavity >5 A away from zinc, and this work highlights three such features: (1) 
      advantageous conformational restraints of a bicyclic 
      thienothiazene-6-sulfonamide-1,1-dioxide inhibitor skeleton in comparison with a 
      monocyclic 2,5-thiophenedisulfonamide skeleton; (2) optimal substituents attached 
      to a secondary sulfonamide group targeted to interact with hydrophobic patches 
      defined by Phe131, Leu198, and Pro202; and (3) optimal stereochemistry and 
      configuration at the C-4 position of bicyclic thienothiazene-6-sulfonamides; the 
      C-4 substituent can interact with His64, the catalytic proton shuttle. 
      Structure-activity relationships rationalize affinity trends observed during the 
      development of brinzolamide (Azopt), the newest carbonic anhydrase inhibitor 
      approved for the treatment of glaucoma.
FAU - Boriack-Sjodin, P A
AU  - Boriack-Sjodin PA
AD  - Department of Chemistry, University of Pennsylvania, Philadelphia 19104-6323, 
      USA.
FAU - Zeitlin, S
AU  - Zeitlin S
FAU - Chen, H H
AU  - Chen HH
FAU - Crenshaw, L
AU  - Crenshaw L
FAU - Gross, S
AU  - Gross S
FAU - Dantanarayana, A
AU  - Dantanarayana A
FAU - Delgado, P
AU  - Delgado P
FAU - May, J A
AU  - May JA
FAU - Dean, T
AU  - Dean T
FAU - Christianson, D W
AU  - Christianson DW
LA  - eng
SI  - PDB/1A42
SI  - PDB/1BN1
SI  - PDB/1BN3
SI  - PDB/1BN4
SI  - PDB/1BNM
SI  - PDB/1BNN
SI  - PDB/1BNQ
SI  - PDB/1BNT
SI  - PDB/1BNU
SI  - PDB/1BNV
SI  - PDB/1BNW
PT  - Journal Article
PL  - United States
TA  - Protein Sci
JT  - Protein science : a publication of the Protein Society
JID - 9211750
RN  - 0 (Carbonic Anhydrase Inhibitors)
RN  - 0 (Sulfonamides)
RN  - EC 4.2.1.1 (Carbonic Anhydrases)
SB  - IM
MH  - Binding Sites
MH  - Carbonic Anhydrase Inhibitors/*chemistry/*metabolism
MH  - Carbonic Anhydrases/*chemistry/*metabolism
MH  - Crystallography, X-Ray
MH  - Humans
MH  - Models, Molecular
MH  - Molecular Structure
MH  - Protein Conformation
MH  - Structure-Activity Relationship
MH  - Sulfonamides/chemistry
PMC - PMC2143894
EDAT- 1998/12/29 00:00
MHDA- 1998/12/29 00:01
PMCR- 1999/06/01
CRDT- 1998/12/29 00:00
PHST- 1998/12/29 00:00 [pubmed]
PHST- 1998/12/29 00:01 [medline]
PHST- 1998/12/29 00:00 [entrez]
PHST- 1999/06/01 00:00 [pmc-release]
AID - 10.1002/pro.5560071201 [doi]
PST - ppublish
SO  - Protein Sci. 1998 Dec;7(12):2483-9. doi: 10.1002/pro.5560071201.