1fy3 | pdb_00001fy3
[G175Q]HBP, A mutant of human heparin binding protein (CAP37)
Structural highlights
Function[CAP7_HUMAN] This is a neutrophil granule-derived antibacterial and monocyte- and fibroblast-specific chemotactic glycoprotein. Binds heparin. The cytotoxic action is limited to many species of Gram-negative bacteria; this specificity may be explained by a strong affinity of the very basic N-terminal half for the negatively charged lipopolysaccharides that are unique to the Gram-negative bacterial outer envelope. It may play a role in mediating recruitment of monocytes in the second wave of inflammation. Has antibacterial activity against the Gram-nagative bacterium P.aeruginosa, this activity is inhibited by LPS from P.aeruginosa. Acting alone, it does not have antimicrobial activity against the Gram-negative bacteria A.actinomycetemcomitans ATCC 29532, A.actinomycetemcomitans NCTC 9709, A.actinomycetemcomitans FDC-Y4, H.aphrophilus ATCC 13252, E.corrodens ATCC 23834, C.sputigena ATCC 33123, Capnocytophaga sp ATCC 33124, Capnocytophaga sp ATCC 27872 or E.coli ML-35. Has antibacterial activity against C.sputigena ATCC 33123 when acting synergistically with either elastase or cathepsin G.[1] [2] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedHeparin 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. 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[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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