Linked Life Data

11170199

Source:http://linkedlifedata.com/resource/pubmed/id/11170199

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2001-2-22
pubmed:abstractText
Heparin binding protein (HBP) is an inactive serine protease homologue with important implications in host defense during infections and inflammations. Two mutants of human HBP, [R23S,F25E]HBP and [G175Q]HBP, have been produced to investigate structure-function relationships of residues in the putative lipid A/lipopolysaccharide (LPS) binding site and BPTI (bovine pancreatic trypsin inhibitor) binding site. The X-ray structures have been determined at 1.9 A resolution for [G175Q]HBP and at 2.5 A resolution for the [R23S,F25E]HBP mutant, and the structures have been fully refined to R-factors of 18.2 % and 20.7 %, respectively. The G175Q mutation does not alter the overall structure of the protein, but the ability to bind BPTI has been eliminated, and the mutant mediates only a limited stimulation of the LPS-induced cytokine release from human monocytes. The lipid A/LPS binding property of [G175Q]HBP is comparable with that of native HBP. The R23S,F25E mutations do not affect the binding of lipid A/LPS and BPTI or the LPS-induced cytokine release from human monocytes. This shows that two diverse ligands, lipid A/LPS and BPTI, do not share binding sites. Previously, there was convincing evidence for the proposed lipid A/LPS binding site of HBP. Unexpectedly, the extensive structural changes introduced by mutation of Arg23 and Phe25 do not affect the binding of lipid A/LPS, indicating that another not yet identified site on HBP is involved in the binding of lipid A/LPS.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0887-3585
pubmed:author
pubmed:copyrightInfo
Copyright 2001 Wiley-Liss, Inc.
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
42
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
442-51
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:11170199-Animals, pubmed-meshheading:11170199-Antimicrobial Cationic Peptides, pubmed-meshheading:11170199-Aprotinin, pubmed-meshheading:11170199-Binding Sites, pubmed-meshheading:11170199-Blood Proteins, pubmed-meshheading:11170199-Carrier Proteins, pubmed-meshheading:11170199-Cattle, pubmed-meshheading:11170199-Crystallization, pubmed-meshheading:11170199-Glycoproteins, pubmed-meshheading:11170199-Humans, pubmed-meshheading:11170199-Interleukin-6, pubmed-meshheading:11170199-Iodine Isotopes, pubmed-meshheading:11170199-Lipid A, pubmed-meshheading:11170199-Lipopolysaccharides, pubmed-meshheading:11170199-Monocytes, pubmed-meshheading:11170199-Protein Conformation, pubmed-meshheading:11170199-Protein Structure, Secondary, pubmed-meshheading:11170199-Recombinant Proteins, pubmed-meshheading:11170199-X-Ray Diffraction
pubmed:year
2001
pubmed:articleTitle
Two mutants of human heparin binding protein (CAP37): toward the understanding of the nature of lipid A/LPS and BPTI binding.
pubmed:affiliation
Department of Medicinal Chemistry, Royal Danish School of Pharmacy, Copenhagen, Denmark. kastrup@medchem.dfh.dk
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't