Document Detail


Structure and mechanism of homoserine kinase: prototype for the GHMP kinase superfamily.
MedLine Citation:
PMID:  11188689     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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 betaalphabeta unit, while the C-terminal domain has a central alpha-beta 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.
Authors:
T Zhou; M Daugherty; N V Grishin; A L Osterman; H Zhang
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Structure (London, England : 1993)     Volume:  8     ISSN:  0969-2126     ISO Abbreviation:  Structure     Publication Date:  2000 Dec 
Date Detail:
Created Date:  2001-01-12     Completed Date:  2001-03-29     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  101087697     Medline TA:  Structure     Country:  England    
Other Details:
Languages:  eng     Pagination:  1247-57     Citation Subset:  IM    
Affiliation:
Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas 75390, USA.
Data Bank Information
Bank Name/Acc. No.:
PDB/1FWK;  1FWL
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MeSH Terms
Descriptor/Qualifier:
Adenosine Diphosphate / metabolism
Amino Acid Sequence
Binding Sites
Catalysis
Crystallography, X-Ray
Dimerization
Galactokinase / chemistry,  metabolism
Hexokinase / chemistry,  metabolism
Humans
Methanococcus / enzymology*
Molecular Sequence Data
Peptide Fragments / chemistry,  metabolism
Phosphotransferases (Alcohol Group Acceptor) / chemistry*,  metabolism*
Protein Structure, Tertiary
Sequence Alignment
Sequence Homology, Amino Acid
Structure-Activity Relationship
Substrate Specificity
Chemical
Reg. No./Substance:
0/Peptide Fragments; 58-64-0/Adenosine Diphosphate; EC 2.7.1.-/Phosphotransferases (Alcohol Group Acceptor); EC 2.7.1.1/Hexokinase; EC 2.7.1.15/ribokinase; EC 2.7.1.36/mevalonate kinase; EC 2.7.1.39/homoserine kinase; EC 2.7.1.6/Galactokinase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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