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| {{STRUCTURE_1fy1| PDB=1fy1 | SCENE= }} | | {{STRUCTURE_1fy1| PDB=1fy1 | SCENE= }} |
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| '''[R23S,F25E]HBP, A MUTANT OF HUMAN HEPARIN BINDING PROTEIN (CAP37)'''
| | ===[R23S,F25E]HBP, A MUTANT OF HUMAN HEPARIN BINDING PROTEIN (CAP37)=== |
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| ==Overview==
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| 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.
| | The line below this paragraph, {{ABSTRACT_PUBMED_11170199}}, adds the Publication Abstract to the page |
| | (as it appears on PubMed at http://www.pubmed.gov), where 11170199 is the PubMed ID number. |
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| | {{ABSTRACT_PUBMED_11170199}} |
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| ==About this Structure== | | ==About this Structure== |
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| [[Category: Stoffer, B.]] | | [[Category: Stoffer, B.]] |
| [[Category: Serine protease homolog]] | | [[Category: Serine protease homolog]] |
| ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 16:53:36 2008'' | | |
| | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 1 04:06:41 2008'' |