Ternary structure reveals mechanism of a membrane diacylglycerol kinase. Nat Commun 2015 Dec 17;6:10140
Date
12/18/2015Pubmed ID
26673816Pubmed Central ID
PMC4703834DOI
10.1038/ncomms10140Scopus ID
2-s2.0-84950268487 (requires institutional sign-in at Scopus site) 33 CitationsAbstract
Diacylglycerol kinase catalyses the ATP-dependent conversion of diacylglycerol to phosphatidic acid in the plasma membrane of Escherichia coli. The small size of this integral membrane trimer, which has 121 residues per subunit, means that available protein must be used economically to craft three catalytic and substrate-binding sites centred about the membrane/cytosol interface. How nature has accomplished this extraordinary feat is revealed here in a crystal structure of the kinase captured as a ternary complex with bound lipid substrate and an ATP analogue. Residues, identified as essential for activity by mutagenesis, decorate the active site and are rationalized by the ternary structure. The γ-phosphate of the ATP analogue is positioned for direct transfer to the primary hydroxyl of the lipid whose acyl chain is in the membrane. A catalytic mechanism for this unique enzyme is proposed. The active site architecture shows clear evidence of having arisen by convergent evolution.
Author List
Li D, Stansfeld PJ, Sansom MSP, Keogh A, Vogeley L, Howe N, Lyons JA, Aragao D, Fromme P, Fromme R, Basu S, Grotjohann I, Kupitz C, Rendek K, Weierstall U, Zatsepin NA, Cherezov V, Liu W, Bandaru S, English NJ, Gati C, Barty A, Yefanov O, Chapman HN, Diederichs K, Messerschmidt M, Boutet S, Williams GJ, Marvin Seibert M, Caffrey MAuthor
Wei Liu PhD Professor in the Pharmacology and Toxicology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Adenosine TriphosphateBinding Sites
Catalytic Domain
Cell Membrane
Crystallography, X-Ray
Diacylglycerol Kinase
Escherichia coli
Models, Molecular
Protein Conformation
