Linked Life Data

11004559

Source:http://linkedlifedata.com/resource/pubmed/id/11004559

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1-2
pubmed:dateCreated
2000-10-30
pubmed:abstractText
Candida yeasts are rarely infectious, but frequently cause life-threatening systemic infections in patients immunocompromised by AIDS or by immunosuppressive therapeutics. The secreted aspartic proteases (Saps) are known virulence factors of pernicious Candida species. The most virulent, Candida albicans, possesses at least nine SAP genes, some of which are specifically expressed from cells with morphologies associated with virulence. Only one of these proteases, Sap2, has been previously purified from yeast in sufficient quantities for enzymic studies. The other enzymes are present in low amounts in yeast culture and are difficult to purify. As a consequence, enzyme properties, including the substrate specificities, of all Saps are poorly studied. Therefore, four Saps that are known to be expressed in C. albicans, Sap1, Sap2, Sap3 and Sap6, were produced in Escherichia coli as recombinant zymogens and purified in large quantities. These proenzymes were autoactivated and purified as active proteases. The enzymic properties including the substrate specificities at the P(1) and P(1)' sites were determined using a competitive hydrolysis method employing synthetic substrate mixtures. All four Saps cleave peptide bonds between larger hydrophobic amino acids, but these somewhat broad specificities differ in detail among the four enzymes at both sites. At the P(1) site, Sap1, Sap2 and Sap6 prefer Phe while Sap3 prefers Leu. Positively charged amino acids are also accommodated, especially by Sap2 and Sap3. The specificities at P(1)' are broader than at P(1) for all four enzymes. Sap6 prefers Ala, whereas other Saps prefer Tyr. Acidic side chains are also accommodated at this site. Analysis of substrates with a hydrophobic amino acid in P(1)' reveals that all the Saps possess a unique preference for Ala at this site. The observed differences of residue preferences among Saps may be utilized for the design of specific substrates and inhibitors.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0006-3002
pubmed:author
pubmed:issnType
Print
pubmed:day
14
pubmed:volume
1480
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
117-31
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
2000
pubmed:articleTitle
Enzymic characteristics of secreted aspartic proteases of Candida albicans.
pubmed:affiliation
Protein Studies Program, Oklahoma Medical Research Foundation, Oklahoma City, OH 73104, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.