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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
4
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pubmed:dateCreated |
1996-10-21
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pubmed:abstractText |
The three-dimensional structure of a secreted aspartic protease from Candida albicans complexed with a potent inhibitor reveals variations on the classical aspartic protease theme that dramatically alter the specificity of this class of enzymes. The structure presents: (1) an 8-residue insertion near the first disulfide (Cys 45-Cys 50, pepsin numbering) that results in a broad flap extending toward the active site; (2) a 7-residue deletion replacing helix hN2 (Ser 110-Tyr 114), which enlarges the S3 pocket; (3) a short polar connection between the two rigid body domains that alters their relative orientation and provides certain specificity; and (4) an ordered 11-residue addition at the carboxy terminus. The inhibitor binds in an extended conformation and presents a branched structure at the P3 position. The implications of these findings for the design of potent antifungal agents are discussed.
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pubmed:grant |
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/8845753-1418819,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8845753-1474437,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8845753-1514700,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8845753-1603805,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8845753-1688827,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8845753-1741614,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8845753-17810339,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8845753-1807356,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8845753-1874000,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8845753-1880680,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8845753-2025413,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8845753-2115087,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8845753-2194475,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8845753-2194852,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8845753-2206206,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8845753-2217165,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8845753-2217166,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8845753-24179,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8845753-2441069,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8845753-2646602,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8845753-2676515,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8845753-3067860,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8845753-3119339,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8845753-3137345,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8845753-323722,
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http://linkedlifedata.com/resource/pubmed/commentcorrection/8845753-7984113,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8845753-8068659,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8845753-8107115,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8845753-8335356,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8845753-8450540,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8845753-8591036,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8845753-8665087
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Apr
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pubmed:issn |
0961-8368
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
5
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
640-52
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pubmed:dateRevised |
2010-9-13
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pubmed:meshHeading |
pubmed-meshheading:8845753-Amino Acid Sequence,
pubmed-meshheading:8845753-Antifungal Agents,
pubmed-meshheading:8845753-Aspartic Acid Endopeptidases,
pubmed-meshheading:8845753-Binding Sites,
pubmed-meshheading:8845753-Candida albicans,
pubmed-meshheading:8845753-Crystallography, X-Ray,
pubmed-meshheading:8845753-Drug Design,
pubmed-meshheading:8845753-Molecular Sequence Data,
pubmed-meshheading:8845753-Protease Inhibitors,
pubmed-meshheading:8845753-Protein Conformation
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pubmed:year |
1996
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pubmed:articleTitle |
Structure of a secreted aspartic protease from C. albicans complexed with a potent inhibitor: implications for the design of antifungal agents.
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pubmed:affiliation |
Laboratory of Protein Crystallography, Abbott Laboratories, Abbott Park, Illinois 60064-3500, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
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