PDBsum entry: 1h73

Transferase

PDB id: 1h73

Contents

Protein chain

296 a.a. *

Ligands

THR

ANP

Waters ×249

* Residue conservation analysis

PDB id:

1h73

Name:

Transferase

Title:

Crystal structure of homoserine kinase complexed with threonine

Structure:

Homoserine kinase. Chain: a. Synonym: hk. Engineered: yes

Source:

Methanococcus jannaschii. Organism_taxid: 2190. Expressed in: escherichia coli. Expression_system_taxid: 562

Biol. unit:

Dimer (from PDB file)

Resolution:

2.00Å R-factor: 0.178 R-free: 0.222

Authors:

S.S.Krishna,T.Zhou,M.Daugherty,A.L.Osterman,H.Zhang

Key ref:

S.S.Krishna et al. (2001). Structural basis for the catalysis and substrate specificity of homoserine kinase. Biochemistry, 40, 10810-10818. PubMed id: 11535056 DOI: 10.1021/bi010851z

Date:

02-Jul-01 Release date: 13-Sep-01

Protein chain

Q58504  (KHSE_METJA) -  Homoserine kinase

Seq: 296 a.a.

Struc: 296 a.a.

Enzyme reactions

• Enzyme class: E.C.2.7.1.39 - Homoserine kinase.
• Pathway: Threonine Biosynthesis
• Reaction: ATP + L-homoserine = ADP + O-phospho-L-homoserine

ATP + L-homoserine (Bound ligand (Het Group name = THR) matches with 66.00% similarity) = ADP (Bound ligand (Het Group name = ANP) matches with 81.00% similarity) + O-phospho-L-homoserine

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

 Gene Ontology (GO) functional annotation 

• Cellular component: cytoplasm (1 term)
• Biological process: phosphorylation (4 terms)
• Biochemical function: nucleotide binding (5 terms)

reference

DOI no: 10.1021/bi010851z

Biochemistry 40:10810-10818 (2001)

PubMed id: 11535056

Structural basis for the catalysis and substrate specificity of homoserine kinase.

S.S.Krishna, T.Zhou, M.Daugherty, A.Osterman, H.Zhang.

ABSTRACT

Homoserine kinase (HSK), the fourth enzyme in the aspartate pathway of amino acid biosynthesis, catalyzes the phosphorylation of L-homoserine (Hse) to L-homoserine phosphate, an intermediate in the production of L-threonine, L-isoleucine, and in higher plants, L-methionine. The high-resolution structures of Methanococcus jannaschii HSK ternary complexes with its amino acid substrate and ATP analogues have been determined by X-ray crystallography. These structures reveal the structural determinants of the tight and highly specific binding of Hse, which is coupled with local conformational changes that enforce the sequestration of the substrate. The delta-hydroxyl group of bound Hse is only 3.4 A away from the gamma-phosphate of the bound nucleotide, poised for the in-line attack at the gamma-phosphorus. The bound nucleotides are flexible at the triphosphate tail. Nevertheless, a Mg(2+) was located in one of the complexes that binds between the beta- and gamma-phosphates of the nucleotide with good ligand geometry and is coordinated by the side chain of Glu130. No strong nucleophile (base) can be located near the phosphoryl acceptor hydroxyl group. Therefore, we propose that the catalytic mechanism of HSK does not involve a catalytic base for activating the phosphoryl acceptor hydroxyl but instead is mediated via a transition state stabilization mechanism.