Structure of HBP, a multifunctional protein with a serine proteinase fold

@article{Iversen1997StructureOH,
  title={Structure of HBP, a multifunctional protein with a serine proteinase fold},
  author={Lars Iversen and Jette Sandholm Kastrup and S{\o}ren Erik Bj{\o}rn and Poul Baad Rasmussen and Finn C. Wiberg and H. J. Flodgaard and Ingrid Kj{\o}ller Larsen},
  journal={Nature Structural Biology},
  year={1997},
  volume={4},
  pages={265-268}
}
The structure of human heparin binding protein reveals that the serine proteinase fold has been used as a scaffold for a multifunctional protein with antibacterial activity, monocyte and t-cell activating properties and endotoxin and heparin binding capacity. 
Identifying the functional part of heparin-binding protein (HBP) as a monocyte stimulator and the novel role of monocytes as HBP producers
TLDR
Normally, HBP production and release is ascribed to neutrophil granulocytes, but here it is found that also monocytes secrete HBP when stimulated with LPS, and a small amount of HBP can be demonstrated when monocytes are incubated in medium alone.
Two mutants of human heparin binding protein (CAP37): Toward the understanding of the nature of lipid A/LPS and BPTI binding
TLDR
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 bindingof lipid A /LPS.
The Crystal Structure of a Novel Mammalian Lectin, Ym1, Suggests a Saccharide Binding Site*
TLDR
Ym1, a secretory protein synthesized by activated murine peritoneal macrophages, is a novel mammalian lectin with a binding specificity to GlcN and shares significant homology with chitinase A of Serratia marcescens, which has a similar carbohydrate binding cleft.
Azurocidin -- inactive serine proteinase homolog acting as a multifunctional inflammatory mediator.
  • W. Wątorek
  • Biology, Chemistry
    Acta biochimica Polonica
  • 2003
TLDR
Azurocidin has a broad spectrum of antimicrobial activity, mainly against Gram-negative bacteria, but is also recognized as a multifunctional inflammatory mediator for its contracting effects on endothelial cells causing an increase of vascular permeability, capacity to bind endotoxin and ability to attract monocytes to inflammation sites.
Azurocidin — inactive serine proteinase homolog acting as a multifunctional inflammatory mediator
TLDR
Azurocidin has a broad spectrum of antimicrobial activity, mainly against Gram-negative bacteria, but is also recognized as a multifunctional inflammatory mediator for its contracting effects on endothelial cells causing an increase of vascular permeability, capacity to bind endotoxin and ability to attract monocytes to inflammation sites.
A CD14 Domain with Lipopolysaccharide‐Binding and ‐Neutralizing Activity
TLDR
Analysis of the structure–activity relationship of this peptide revealed that leucines 87, 91, and 94 are essential for these activities and provided a basis for the generation of highly soluble analogues with stronger lipopolysaccharide‐neutralizing activity.
Atomic resolution structure of human HBP/CAP37/azurocidin.
TLDR
A putative protein kinase C activation site has been identified, involving residues 113-120, and the structure is compared to the previously determined 2.3 A resolution structure of HBP.
Structural and energetic determinants of the S1-site specificity in serine proteases.
TLDR
This review is concerned mainly with primary structural determinants of the S1 specificity, the crucial component of substrate selectivity, often in relation to more distant specificity elements, which cooperatively influence the S 1 site.
Basic Residues in Azurocidin/HBP Contribute to Both Heparin Binding and Antimicrobial Activity*
TLDR
It is reported that the 8 basic residues that were altered in the Loop 3/Loop 4 mutant contribute to the ability of the wild-type azurocidin molecule to bind heparin and to kill E. coli and C. albicans.
Characterization of the biosynthesis, processing, and sorting of human HBP/CAP37/azurocidin
TLDR
This investigation is an important addition to the previous studies on related azurophil granule proteins, and provides novel information concerning the biosynthesis and distinctive amino‐terminal processing of human azurocidin.
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TLDR
The structural features of synthetic peptides that bind to lipid A with high affinity, detoxify LPS in vitro, and prevent LPS-induced cytokine release and lethality in vivo were defined and may provide a strategy for prophylaxis and treatment of L PS-mediated diseases.
Characterization of the structural elements in lipid A required for binding of a recombinant fragment of bactericidal/permeability-increasing protein rBPI23
TLDR
Results demonstrate that rBPI23 has a binding specificity for the lipid A region of LPS and binding involves both electrostatic and hydrophobic components.
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TLDR
A synthetic peptide, amino acid sequence NQGRHFCGGALIHARFVMTAASCFQ, based on residues 20-44 of CAP37 protein mimics its antibiotic and lipopolysaccharide binding action, and should provide new insight into the mechanism of antimicrobial activity ofCAP37.
Covalent structure of two novel neutrophile leucocyte-derived proteins of porcine and human origin. Neutrophile elastase homologues with strong monocyte and fibroblast chemotactic activities.
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Modelling and alignment studies unveil a close relationship of both proteins to the serine protease family, the greatest similarity being to those serines present in granules from peripheral blood cells.
CAP37, a neutrophil‐derived multifunctional inflammatory mediator
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TLDR
The identification of functional peptides should provide new insight into the mechanisms of endotoxin binding, antimicrobial activity, and chemotaxis and in the long term provide key insights into therapies for treating infections and endotoxic shock.
CAP37, a human neutrophil-derived chemotactic factor with monocyte specific activity.
TLDR
It is proposed that CAP37 released from neutrophils during phagocytosis and degranulation may mediate recruitment of monocytes in the second wave of inflammation.
Sperm immobilizing activity of a synthetic bioactive peptide 20-44 of 37-kDa cationic antimicrobial protein (CAP37) of human neutrophils.
TLDR
It is established that motile human sperm are sensitive to CAP37 or its synthetic bioactive peptide and suggested that this protein could play a role in neutrophil-mediated immune destruction of sperm in the female genital tract.
Late intraphagosomal hydrogen ion concentration favors the in vitro antimicrobial capacity of a 37-kilodalton cationic granule protein of human neutrophil granulocytes.
TLDR
Results suggest that 37K CAP may contribute significantly to the ability of PMN to kill gram-negative bacteria by nonoxidative means, particularly as the maturing phagolysosome becomes acidified.
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