Linked Life Data

12873509

Source:http://linkedlifedata.com/resource/pubmed/id/12873509

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
16
pubmed:dateCreated
2003-7-22
pubmed:abstractText
The X-ray crystal structure for the adduct of human carbonic anhydrase II (hCA II) with 4-(4-sulfamoylphenylcarboxamidoethyl)benzenesulfonamide, a topically acting antiglaucoma sulfonamide has been resolved at a resolution of 1.8 A. Its binding to the enzyme is similar with that of other sulfonamides, considering the interactions of the sulfonamide zinc anchoring group, but differs considerably when the organic part of the inhibitor is analyzed. This part of the inhibitor interacts only within the hydrophobic half of the CA active site, leaving the hydrophilic half able to accomodate several water molecules not present in the uncomplexed enzyme. Furthermore, the second head (sulfonamide moiety) participates in two strong hydrogen bonds with amino acid residues (Gly 132 and Gln 136) situated on the rim of the entrance to the active site cleft. Thus, the answer to the question in the title of this paper is that two heads are better than one, since the two sulfamoyl moieties of the inhibitor allow its proper orientation within the active site, with only one head binding in ionized form to the zinc ion, the organic part lying within the hydrophobic half of the active site, and the terminal, carboxamido containing phenylsulfamoyl head participating in strong hydrogen bonds with amino acid residues located at the entrance of it. All these findings are important for the design of better carboxamido CA inhibitors with applications in clinical medicine.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0960-894X
pubmed:author
pubmed:issnType
Print
pubmed:day
18
pubmed:volume
13
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2759-63
pubmed:dateRevised
2004-11-17
pubmed:meshHeading
pubmed:year
2003
pubmed:articleTitle
Carbonic anhydrase inhibitors: X-ray crystallographic structure of the adduct of human isozyme II with a bis-sulfonamide-two heads are better than one?
pubmed:affiliation
Università degli Studi di Firenze, Polo Scientifico, Dipartimento di Chimica, Laboratorio di Chimica Bioinorganica, Via della Lastruccia, 3, Rm 188, I-50019 (Firenze), Sesto Fiorentino, Italy.
pubmed:publicationType
Journal Article