Linked Life Data

12581647

Source:http://linkedlifedata.com/resource/pubmed/id/12581647

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2003-2-12
pubmed:databankReference
pubmed:abstractText
Binding of cystatin-type inhibitors to papain-like exopeptidases cannot be explained by the stefin B-papain complex. The crystal structure of human stefin A bound to an aminopeptidase, porcine cathepsin H, has been determined in monoclinic and orthorhombic crystal forms at 2.8A and 2.4A resolutions, respectively. The asymmetric unit of each form contains four complexes. The structures are similar to the stefin B-papain complex, but with a few distinct differences. On binding, the N-terminal residues of stefin A adopt the form of a hook, which pushes away cathepsin H mini-chain residues and distorts the structure of the short four residue insertion (Lys155A-Asp155D) unique to cathepsin H. Comparison with the structure of isolated cathepsin H shows that the rims of the cathepsin H structure are slightly displaced (up to 1A) from their position in the free enzyme. Furthermore, comparison with the stefin B-papain complex showed that molecules of stefin A bind about 0.8A deeper into the active site cleft of cathepsin H than stefin B into papain. The approach of stefin A to cathepsin H induces structural changes along the interaction surface of both molecules, whereas no such changes were observed in the stefin B-papain complex. Carboxymethylation of papain seems to have prevented the formation of the genuine binding geometry between a papain-like enzyme and a cystatin-type inhibitor as we observe it in the structure presented here.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0022-2836
pubmed:author
pubmed:issnType
Print
pubmed:day
21
pubmed:volume
326
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
875-85
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
2003
pubmed:articleTitle
Crystal structure of Stefin A in complex with cathepsin H: N-terminal residues of inhibitors can adapt to the active sites of endo- and exopeptidases.
pubmed:affiliation
Department of Biochemistry and Molecular Biology, Jozef Stefan Institute, Jamova 39, SI-1111 Ljubljana, Slovenia.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't