1fy1 | pdb_00001fy1
[R23S,F25E]HBP, A MUTANT OF HUMAN HEPARIN BINDING PROTEIN (CAP37)
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Overview
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.
About this Structure
1FY1 is a Single protein structure of sequence from Homo sapiens with NAG and EOH as ligands. Full crystallographic information is available from OCA.
Reference
Two mutants of human heparin binding protein (CAP37): toward the understanding of the nature of lipid A/LPS and BPTI binding., Kastrup JS, Linde V, Pedersen AK, Stoffer B, Iversen LF, Larsen IK, Rasmussen PB, Flodgaard HJ, Bjorn SE, Proteins. 2001 Mar 1;42(4):442-51. PMID:11170199
Page seeded by OCA on Fri Feb 15 15:49:43 2008
