Document Detail


Active site contribution to specificity of the aspartic proteases plasmepsins I and II.
MedLine Citation:
PMID:  12189138     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Pilaiwan Siripurkpong; Jirundon Yuvaniyama; Prapon Wilairat; Daniel E Goldberg
Related Documents :
23625978 - Expression of aberrant hla-b27 molecules is dependent on b27 dosage and peptide supply.
6296088 - Specific receptor sites for pyridoxal 5'-phosphate and pyridoxal 5'-deoxymethylenephosp...
22983148 - Enhancement of gene silencing effect and membrane permeability by peptide-conjugated 27...
24422448 - Isoform-selective disruption of akap-localized pka using hydrocarbon stapled peptides.
18154308 - Template-assembled triple-helical peptide molecules: mimicry of collagen by molecular a...
2364078 - Kinetics of arginine-vasopressin uptake at the blood-brain barrier.
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.     Date:  2002-08-19
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  277     ISSN:  0021-9258     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2002 Oct 
Date Detail:
Created Date:  2002-10-25     Completed Date:  2002-12-09     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  41009-13     Citation Subset:  IM    
Affiliation:
Department of Biochemistry, Faculty of Science, Mahidol University, Rama VI Road, Bangkok 10400, Thailand.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Aspartic Acid Endopeptidases / antagonists & inhibitors,  chemistry,  genetics,  metabolism*
Base Sequence
Binding Sites
Chromatography, High Pressure Liquid
DNA Primers
Hemoglobins / metabolism
Hydrolysis
Models, Molecular
Mutagenesis, Site-Directed
Protozoan Proteins
Recombinant Proteins / antagonists & inhibitors,  chemistry,  genetics,  metabolism
Substrate Specificity
Grant Support
ID/Acronym/Agency:
AI 47798/AI/NIAID NIH HHS
Chemical
Reg. No./Substance:
0/DNA Primers; 0/Hemoglobins; 0/Protozoan Proteins; 0/Recombinant Proteins; EC 3.4.23.-/Aspartic Acid Endopeptidases; EC 3.4.23.38/plasmepsin; EC 3.4.23.39/plasmepsin II

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Conformational changes of calpain from human erythrocytes in the presence of Ca2+.
Next Document:  Alanine-scanning mutagenesis of alpha-helix D segment of interleukin-13 reveals new functionally imp...