PMID- 7608893
OWN - NLM
STAT- MEDLINE
DCOM- 19950817
LR  - 20190709
IS  - 0022-2623 (Print)
IS  - 0022-2623 (Linking)
VI  - 38
IP  - 13
DP  - 1995 Jun 23
TI  - Secondary interactions significantly removed from the sulfonamide binding pocket 
      of carbonic anhydrase II influence inhibitor binding constants.
PG  - 2286-91
AB  - A series of competitive inhibitors of carbonic anhydrase II (CAII; EC 4.2.1.1) 
      that consists of oligo(ethylene glycol) units attached to p-benzenesulfonamides 
      with pendant amino acids, H2NSO2C6H4CONHCH2CH2OCH2CH2OCH2CH2NHCOCHRNH3+, have 
      been synthesized and examined using competitive fluorescence assays. Three of the 
      strongest inhibitors, designated EG3NH3+, EG3GlyNH3+, and EG3PheNH3+, have been 
      studied by X-ray crystallographic methods at limiting resolutions of 1.9, 2.0, 
      and 2.3 A, respectively. The sulfonamide-zinc binding modes and the association 
      of the ethylene glycol linkers to the hydrophobic patch of the active site are 
      similar in all three inhibitors. Differences in the values of Kd are therefore 
      not due to differences in zinc coordination or to differences in the modes of 
      enzyme-glycol association but instead appear to arise from interaction of the 
      pendant amino acids with the surface of the protein. These pendant groups are, 
      however, not sufficiently ordered to be visible in electron density maps. Thus, 
      structural variations of inhibitors at locations distant from the primary binding 
      (i.e., the sulfonamide group) site affect the overall binding affinities of 
      inhibitors (e.g., Kd (EG3PheNH3+) = 14 nM as compared with Kd (EG3GluNH3+) = 100 
      nM).
FAU - Boriack, P A
AU  - Boriack PA
AD  - Department of Chemistry, University of Pennsylvania, Philadelphia 19104-6323, 
      USA.
FAU - Christianson, D W
AU  - Christianson DW
FAU - Kingery-Wood, J
AU  - Kingery-Wood J
FAU - Whitesides, G M
AU  - Whitesides GM
LA  - eng
GR  - GM 30367/GM/NIGMS NIH HHS/United States
GR  - GM 45614/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Med Chem
JT  - Journal of medicinal chemistry
JID - 9716531
RN  - 0 (Carbonic Anhydrase Inhibitors)
RN  - 0 (Sulfonamides)
RN  - EC 4.2.1.1 (Carbonic Anhydrases)
SB  - IM
MH  - Animals
MH  - Carbonic Anhydrase Inhibitors/chemistry/*metabolism
MH  - Carbonic Anhydrases/chemistry/*metabolism
MH  - Cattle
MH  - Crystallography, X-Ray
MH  - Molecular Conformation
MH  - Protein Binding
MH  - Sulfonamides/chemistry/*metabolism
EDAT- 1995/06/23 00:00
MHDA- 1995/06/23 00:01
CRDT- 1995/06/23 00:00
PHST- 1995/06/23 00:00 [pubmed]
PHST- 1995/06/23 00:01 [medline]
PHST- 1995/06/23 00:00 [entrez]
AID - 10.1021/jm00013a004 [doi]
PST - ppublish
SO  - J Med Chem. 1995 Jun 23;38(13):2286-91. doi: 10.1021/jm00013a004.