PDBsum entry 1hkc

Phosphotransferase

PDB id: 1hkc

Contents

Protein chain

899 a.a. *

Ligands

BGC

PO4 ×2

Metals

__K ×2

Waters ×150

* Residue conservation analysis

PDB id:

1hkc

Name:

Phosphotransferase

Title:

Recombinant human hexokinase type i complexed with glucose and phosphate

Structure:

D-glucose 6-phosphotransferase. Chain: a. Synonym: hexokinase i, hexokinase type i, human brain hexokinase. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Cell_line: bl21. Organ: brain. Cellular_location: cytoplasm surface of mitochondria. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.

Biol. unit:

Monomer (from PDB file)

Resolution:

2.80Å R-factor: 0.174 R-free: 0.241

Authors:

A.E.Aleshin,R.B.Honzatko

Key ref:

A.E.Aleshin et al. (1998). Regulation of hexokinase I: crystal structure of recombinant human brain hexokinase complexed with glucose and phosphate. J Mol Biol, 282, 345-357. PubMed id: 9735292 DOI: 10.1006/jmbi.1998.2017

Date:

01-Jul-98 Release date: 11-Nov-98

Protein chain

P19367  (HXK1_HUMAN) -  Hexokinase-1 from Homo sapiens

Seq: 917 a.a.

Struc: 899 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

Enzyme reactions

• Enzyme class: E.C.2.7.1.1 - hexokinase.
• Reaction: a D-hexose + ATP = a D-hexose 6-phosphate + ADP + H⁺

D-hexose + ATP (Bound ligand (Het Group name = BGC) corresponds exactly) = D-hexose 6-phosphate + ADP + H(+)

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

reference

DOI no: 10.1006/jmbi.1998.2017

J Mol Biol 282:345-357 (1998)

PubMed id: 9735292

Regulation of hexokinase I: crystal structure of recombinant human brain hexokinase complexed with glucose and phosphate.

A.E.Aleshin, C.Zeng, H.D.Bartunik, H.J.Fromm, R.B.Honzatko.

ABSTRACT

Hexokinase I, the pacemaker of glycolysis in brain tissue and red blood cells, is comprised of two similar domains fused into a single polypeptide chain. The C-terminal half of hexokinase I is catalytically active, whereas the N-terminal half is necessary for the relief of product inhibition by phosphate. A crystalline complex of recombinant human hexokinase I with glucose and phosphate (2.8 A resolution) reveals a single binding site for phosphate and glucose at the N-terminal half of the enzyme. Glucose and phosphate stabilize the N-terminal half in a closed conformation. Unexpectedly, glucose binds weakly to the C-terminal half of the enzyme and does not by itself stabilize a closed conformation. Evidently a stable, closed C-terminal half requires either ATP or glucose 6-phosphate along with glucose. The crystal structure here, in conjunction with other studies in crystallography and directed mutation, puts the phosphate regulatory site at the N-terminal half, the site of potent product inhibition at the C-terminal half, and a secondary site for the weak interaction of glucose 6-phosphate at the N-terminal half of the enzyme. The relevance of crystal structures of hexokinase I to the properties of monomeric hexokinase I and oligomers of hexokinase I bound to the surface of mitochondria is discussed.

Selected figure(s)

Figure 1.
Figure 1. Stereoview of a single polypeptide chain in the glucose/P[i] dimer of hexokinase I. Residue 465 separates the N and C-terminal halves. The color code is as follows, yellow, small domains (residues 75 to 209, 448 to 465 and residues 523 to 657, 896 to 913); light purple, large domains (residues 13 to 74, 210 to 447 and residues 466 to 522, 658 to 895); dark purple, segments participating in intrachain salt links (residues 242 to 250, 796 to 813); blue, bound glucose; red, bound phosphate; green, bound metal ions. The view is perpendicular to the dimer 2-fold axis. Drawing made using MOLSCRIPT [Kraulis 1991].

Figure 9.
Figure 9. Superposition of a model for hexokinase I with the N-terminal half in an open conformation (bold lines) onto the glucose/P[i] complex, using the small domain of the N-terminal half as a basis for the superposition. The transition from a closed to an opened conformation moves the large domain of the N-terminal half relative to the remainder of the enzyme and should influence contacts between the N and C-terminal halves.

The above figures are reprinted by permission from Elsevier: J Mol Biol (1998, 282, 345-357) copyright 1998.

Figures were selected by an automated process.