Structure and mechanism of homoserine kinase: Prototype for the GHMP kinase superfamily

T. Zhou, M. Daugherty, N. V. Grishin, A. L. Osterman, H. Zhang

Research output: Contribution to journalArticlepeer-review

108 Scopus citations


Background: Homoserine kinase (HSK) catalyzes an important step in the threonine biosynthesis pathway. It belongs to a large yet unique class of small metabolite kinases, the GHMP kinase superfamily. Members in the GHMP superfamily participate in several essential metabolic pathways, such as amino acid biosynthesis, galactose metabolism, and the mevalonate pathway. Results: The crystal structure of HSK and its complex with ADP reveal a novel nucleotide binding fold. The N-terminal domain contains an unusual left-handed βαβ unit, while the C-terminal domain has a central α-β plait fold with an insertion of four helices. The phosphate binding loop in HSK is distinct from the classical P loops found in many ATP/GTP binding proteins. The bound ADP molecule adopts a rare syn conformation and is in the opposite orientation from those bound to the P loop-containing proteins. Inspection of the substrate binding cavity indicates several amino acid residues that are likely to be involved in substrate binding and catalysis. Conclusions: The crystal structure of HSK is the first representative in the GHMP superfamily to have determined structure. It provides insight into the structure and nucleotide binding mechanism of not only the HSK family but also a variety of enzymes in the GHMP superfamily. Such enzymes include galactokinases, mevalonate kinases, phosphomevalonate kinases, mevalonate pyrophosphate decarboxylases, and several proteins of yet unknown functions.

Original languageEnglish (US)
Pages (from-to)1247-1257
Number of pages11
Issue number12
StatePublished - 2000


  • ATP binding
  • GHMP kinases
  • Homoserine kinase
  • Phosphate-binding loop

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology


Dive into the research topics of 'Structure and mechanism of homoserine kinase: Prototype for the GHMP kinase superfamily'. Together they form a unique fingerprint.

Cite this