PDBsum entry: 1bht

Heparin-binding domain

PDB-id: 1bht

Biological unit* = asymmetric unit, as shown
(*as deduced by PQS)

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Description

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References

PROCHECK

Protein chains

176 a.a. *

Ligands

SO4 ×3

EPE ×2

Waters ×266

* Residue conservation analysis

Tools

Clefts Calculation

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PDB id:

1bht

Name:

Heparin-binding domain

Title:

Nk1 fragment of human hepatocyte growth factor

Structure:

Hepatocyte growth factor. Chain: a, b. Fragment: nk1 fragment, heparin binding domain plus c-met binding domain. Synonym: nk1. Engineered: yes. Other_details: hepes buffer molecule bound in kringle binding pocket

Source:

Homo sapiens. Human. Organism_taxid: 9606. Cellular_location: cytoplasm. Expressed in: escherichia coli. Expression_system_taxid: 562.

Biological unit:

Dimer (from PQS)

UniProt:

Chains A, B: P14210 (HGF_HUMAN)

Seq:

Struc:

Seq:

Struc:

Seq:

728 a.a.

Struc:

176 a.a.

Key:	PfamA domain
Secondary structure	CATH domain

Resolution:

2.00Å

R-factor:

0.196

R-free:

0.247

Authors:

M.H.Ultsch,N.A.Lokker,P.J.Godowski,A.M.De Vos

Key ref:

M.Ultsch et al. (1998). Crystal structure of the NK1 fragment of human hepatocyte growth factor at 2.0 A resolution.. Structure, 6, 1383-1393. [PubMed id: 9817840] [DOI: 10.1016/S0969-2126(98)00138-5]

Date:

10-Jun-98

Release date:

04-Nov-98

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Clefts

Surface

Key reference

DOI no: 10.1016/S0969-2126(98)00138-5

Structure 6:1383-1393 (1998)

PubMed id: 9817840

Crystal structure of the NK1 fragment of human hepatocyte growth factor at 2.0 A resolution.

M.Ultsch, N.A.Lokker, P.J.Godowski, A.M.de Vos.

ABSTRACT

BACKGROUND: Hepatocyte growth factor (HGF) is a mitogen for hepatocytes and has also been implicated as an epithelial morphogen in tumor invasion. HGF activates its specific cellular receptor, c-met, through an aggregation mechanism potentiated by heparan sulfate glycosaminoglycans. HGF consists of an N-terminal (N) domain, four kringle domains (the first of which carries receptor-binding determinants), and an inactive serine-protease-like domain. NK1, a naturally occurring fragment of HGF, acts as an antagonist of HGF in the absence of heparin. RESULTS: The N domain of NK1 consists of a central five-stranded antiparallel beta sheet flanked by an alpha helix and a two-stranded beta ribbon. The overall N domain structure in the context of the NK1 fragment is similar to the structure of the isolated domain; two lysines and an arginine residue coordinate a bound sulfate ion. The NK1 kringle domain is homologous to kringle 4 from plasminogen, except that the lysine-binding pocket is altered by the insertion of a glycine residue. Here, a HEPES molecule is bound in the pocket. The asymmetric unit of the crystal contains a 'head-to-tail' NK1 dimer. We use this dimer to propose a model of the NK2 fragment of HGF. CONCLUSIONS: A cluster of exposed lysine and arginine residues in or near the hairpin-loop region of the N domain might form part of the NK1 heparin-binding site. In our NK2 model, both kringle domains pack loosely against the N domain, and a long, positively charged groove lines the interface. This groove might be involved in glycosaminoglycan binding. The HGF receptor-binding determinants are clustered near the binding pocket of the first kringle domain, opposite the N domain.

Selected figure(s)

Figure 4.
Figure 4. Stereoview of the intramolecular interface between the N domain (green) and the kringle domain (yellow) around the salt bridge between Lys43 and Asp171. Water molecules are shown as red spheres, and hydrogen bonds are represented by dashed lines.

The above figure is reprinted by permission from Cell Press: Structure (1998, 6, 1383-1393) copyright 1998.

Figure was selected by an automated process.