1FY3

[G175Q]HBP, A mutant of human heparin binding protein (CAP37)

1FY3 の概要

• エントリーDOI: 10.2210/pdb1fy3/pdb
• 関連するPDBエントリー: 1A7S 1AE5 1FY1
• 分子名称: HEPARIN-BINDING PROTEIN, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (6 entities in total)
• 機能のキーワード: serine protease homolog, bpti binding site, antimicrobial protein
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 25100.68

構造登録者

Kastrup, J.S.,Linde, V.,Pedersen, A.K.,Stoffer, B.,Iversen, L.F.,Larsen, I.K.,Rasmussen, P.B.,Flodgaard, H.J.,Bjorn, S.E. (登録日: 2000-09-28, 公開日: 2001-09-28, 最終更新日: 2024-11-20)

主引用文献

Kastrup, J.S.,Linde, V.,Pedersen, A.K.,Stoffer, B.,Iversen, L.F.,Larsen, I.K.,Rasmussen, P.B.,Flodgaard, H.J.,Bjorn, S.E.
Two mutants of human heparin binding protein (CAP37): toward the understanding of the nature of lipid A/LPS and BPTI binding.
Proteins, 42:442-451, 2001

PubMed Abstract: 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: 11170199
DOI: 10.1002/1097-0134(20010301)42:4<442::AID-PROT30>3.0.CO;2-S

実験手法

X-RAY DIFFRACTION (1.89 Å)