1eag: Difference between revisions
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==Overview== | ==Overview== | ||
BACKGROUND: Infections caused by Candida albicans, a common fungal, pathogen of humans, are increasing in incidence, necessitating development, of new therapeutic drugs. Secreted aspartic proteinase (SAP) activity is, considered an important virulence factor in these infections and might, offer a suitable target for drug design. Amongst the various SAP isozymes, the SAP2 gene product is the major form expressed in a number of C., albicans strains. RESULTS: The three-dimensional structures of SAP2, complexed with the tight-binding inhibitor A70450 (a synthetic hexapeptide, analogue) and with the general aspartic proteinase inhibitor pepstatin A, (a microbial natural product) have been determined to 2.1 A and 3.0 A, resolution, respectively. Although the protein structure retains the main, .. | BACKGROUND: Infections caused by Candida albicans, a common fungal, pathogen of humans, are increasing in incidence, necessitating development, of new therapeutic drugs. Secreted aspartic proteinase (SAP) activity is, considered an important virulence factor in these infections and might, offer a suitable target for drug design. Amongst the various SAP isozymes, the SAP2 gene product is the major form expressed in a number of C., albicans strains. RESULTS: The three-dimensional structures of SAP2, complexed with the tight-binding inhibitor A70450 (a synthetic hexapeptide, analogue) and with the general aspartic proteinase inhibitor pepstatin A, (a microbial natural product) have been determined to 2.1 A and 3.0 A, resolution, respectively. Although the protein structure retains the main, features of a typical aspartic proteinase, it also shows some significant, differences, due mainly to several sequence insertions and deletions (as, revealed by homology modelling), that alter the shape of the binding, cleft. There is also considerable variation in the C-terminal structural, domain. CONCLUSIONS: The differences in side chains, and in the, conformations adopted by the two inhibitors, particularly at their P4, P3, and P'2 positions (using standard notation for protease-inhibitor, residues), allows the A70450 structure to complement, more accurately, that of the substrate-binding site of SAP2. Some differences in the, binding clefts of other SAP isoenzymes may be deduced from the SAP2, structure. | ||
==About this Structure== | ==About this Structure== | ||
1EAG is a | 1EAG is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Candida_albicans Candida albicans] with ODS and VAS as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Candidapepsin Candidapepsin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.23.24 3.4.23.24] Structure known Active Site: CAT. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1EAG OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: sap2]] | [[Category: sap2]] | ||
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Revision as of 13:59, 5 November 2007
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SECRETED ASPARTIC PROTEINASE (SAP2) FROM CANDIDA ALBICANS COMPLEXED WITH A70450
OverviewOverview
BACKGROUND: Infections caused by Candida albicans, a common fungal, pathogen of humans, are increasing in incidence, necessitating development, of new therapeutic drugs. Secreted aspartic proteinase (SAP) activity is, considered an important virulence factor in these infections and might, offer a suitable target for drug design. Amongst the various SAP isozymes, the SAP2 gene product is the major form expressed in a number of C., albicans strains. RESULTS: The three-dimensional structures of SAP2, complexed with the tight-binding inhibitor A70450 (a synthetic hexapeptide, analogue) and with the general aspartic proteinase inhibitor pepstatin A, (a microbial natural product) have been determined to 2.1 A and 3.0 A, resolution, respectively. Although the protein structure retains the main, features of a typical aspartic proteinase, it also shows some significant, differences, due mainly to several sequence insertions and deletions (as, revealed by homology modelling), that alter the shape of the binding, cleft. There is also considerable variation in the C-terminal structural, domain. CONCLUSIONS: The differences in side chains, and in the, conformations adopted by the two inhibitors, particularly at their P4, P3, and P'2 positions (using standard notation for protease-inhibitor, residues), allows the A70450 structure to complement, more accurately, that of the substrate-binding site of SAP2. Some differences in the, binding clefts of other SAP isoenzymes may be deduced from the SAP2, structure.
About this StructureAbout this Structure
1EAG is a Single protein structure of sequence from Candida albicans with ODS and VAS as ligands. Active as Candidapepsin, with EC number 3.4.23.24 Structure known Active Site: CAT. Full crystallographic information is available from OCA.
ReferenceReference
The crystal structure of a major secreted aspartic proteinase from Candida albicans in complexes with two inhibitors., Cutfield SM, Dodson EJ, Anderson BF, Moody PC, Marshall CJ, Sullivan PA, Cutfield JF, Structure. 1995 Nov 15;3(11):1261-71. PMID:8591036
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