Structural basis for selective inhibition of cyclooxygenase-2 by anti-inflammatory agents
Article Abstract:
The structures of unliganded murine cyclooxygenase-1 and -2 (COX-1 and COX-2) and those of complexes with flurbiprofen, indomethacin and SC-558, a selective COX-2 inhibitor, were studied using crystallography and molecular replacement methods. The results indicated that the overall structures of COX-1 and COX-2 are highly conserved although COX-2 was shown to have a much larger non-steroidal anti-inflammatory drug binding site due to the substitution of a valine for isoleucine in the active site. It was also evident that the time-dependent cyclooxygenase inhibition may proceed via more than one mechanism.
Publication Name: Nature
Subject: Zoology and wildlife conservation
ISSN: 0028-0836
Year: 1996
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Unique fold and active site in cytomegalovirus protease
Article Abstract:
The crystal structure of human cytomegalovirus (CMV) protease at 2.5 resolution shows that this serine protease has a catalytic triad consisting of histidine as a third member. The fold and catalytic site are different from those in other serine proteases. Analysis also reveals a characteristic dimer interface that is important for the protease activity. Human CMV protease is a pathogen that can cause fatal infections in congenitally infected infants, immunocompromised individuals and transplant patients.
Publication Name: Nature
Subject: Zoology and wildlife conservation
ISSN: 0028-0836
Year: 1996
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Three-dimensional structure of human cytomegalovirus protease
Article Abstract:
The three dimensional structure of human cytomegalovirus protease at 2.27 resolution reveals an unique fold and a catalytic method for cleavage. The monomer fold of the enzyme has a seven-stranded beta-barrel encircled by a chain of helixes that form the carboxy terminus of the molecule. The histidine residues at positions 63 and 157 activate the serine nucleophile at position 132. Dimerization in the molecule imparts specificity and recognition in the substrate binding activity.
Publication Name: Nature
Subject: Zoology and wildlife conservation
ISSN: 0028-0836
Year: 1996
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