Linked Life Data

12189138

Source:http://linkedlifedata.com/resource/pubmed/id/12189138

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
43
pubmed:dateCreated
2002-10-25
pubmed:abstractText
Plasmepsins I and II (PM I and II) are aspartic proteases involved in the initial steps of Plasmodium hemoglobin degradation. They are attractive targets for antimalarial drug development. The two enzymes are 73% identical, yet have different substrate and inhibitor specificities. The x-ray structures of proform and mature PM II have been determined, but models of PM I do not adequately explain the selectivity of the two proteases. To better understand the basis of these recognition differences, we have identified nine residues of PM II that are in proximity to the inhibitor pepstatin in the crystal structure and differ in PM I. We mutated these residues in PM II to the cognate amino acids of PM I. Kinetic parameters for substrate and inhibitors for the PM II-mutant were similar to those of PM II-wild type (WT). Cleavage specificity was assessed using hemoglobin or a random decamer peptide library as substrate. Again, PM II-mutant behaved like PM II-WT rather than PM I-WT. These results indicate that differences in plasmepsin specificity depend more on conformational differences from distant sites than on specific active site variation.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
25
pubmed:volume
277
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
41009-13
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
2002
pubmed:articleTitle
Active site contribution to specificity of the aspartic proteases plasmepsins I and II.
pubmed:affiliation
Department of Biochemistry, Faculty of Science, Mahidol University, Rama VI Road, Bangkok 10400, Thailand.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't