Role of Motif III in Catalysis by Acetyl-CoA Synthetase

Overview

Journal Archaea

Specialty Microbiology

Date 2012 Sep 14

PMID 22973162

Citations 2

Authors

Cheryl Ingram-Smith

Jerry L Thurman Jr

Karen Zimowski

Kerry S Smith

Affiliations

Soon will be listed here.

Abstract

The acyl-adenylate-forming enzyme superfamily, consisting of acyl- and aryl-CoA synthetases, the adenylation domain of the nonribosomal peptide synthetases, and luciferase, has three signature motifs (I-III) and ten conserved core motifs (A1-A10), some of which overlap the signature motifs. The consensus sequence for signature motif III (core motif A7) in acetyl-CoA synthetase is Y-X-S/T/A-G-D, with an invariant fifth position, highly conserved first and fourth positions, and variable second and third positions. Kinetic studies of enzyme variants revealed that an alteration at any position resulted in a strong decrease in the catalytic rate, although the most deleterious effects were observed when the first or fifth positions were changed. Structural modeling suggests that the highly conserved Tyr in the first position plays a key role in active site architecture through interaction with a highly conserved active-site Gln, and the invariant Asp in the fifth position plays a critical role in ATP binding and catalysis through interaction with the 2'- and 3'-OH groups of the ribose moiety. Interactions between these Asp and ATP are observed in all structures available for members of the superfamily, consistent with a critical role in substrate binding and catalysis for this invariant residue.

Citing Articles

The Roles of Coenzyme A Binding Pocket Residues in Short and Medium Chain Acyl-CoA Synthetases.

Meng Y, Ingram-Smith C, Ahmed O, Smith K Life (Basel). 2023; 13(8).

PMID: 37629500 PMC: 10455477. DOI: 10.3390/life13081643.

Characterization and expression of AMP-forming Acetyl-CoA Synthetase from Dunaliella tertiolecta and its response to nitrogen starvation stress.

Liang M, Qv X, Jin H, Jiang J Sci Rep. 2016; 6:23445.

PMID: 27025661 PMC: 4812251. DOI: 10.1038/srep23445.

References

Zhang Z, Zhou R, Sauder J, Tonge P, Burley S, Swaminathan S . Structural and functional studies of fatty acyl adenylate ligases from E. coli and L. pneumophila. J Mol Biol. 2010; 406(2):313-24. PMC: 3040979. DOI: 10.1016/j.jmb.2010.12.011. View

Osman K, Du L, He Y, Luo Y . Crystal structure of Bacillus cereus D-alanyl carrier protein ligase (DltA) in complex with ATP. J Mol Biol. 2009; 388(2):345-55. DOI: 10.1016/j.jmb.2009.03.040. View

Du L, He Y, Luo Y . Crystal structure and enantiomer selection by D-alanyl carrier protein ligase DltA from Bacillus cereus. Biochemistry. 2008; 47(44):11473-80. DOI: 10.1021/bi801363b. View

Bradford M . A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976; 72:248-54. DOI: 10.1016/0003-2697(76)90527-3. View

Gulick A . Conformational dynamics in the Acyl-CoA synthetases, adenylation domains of non-ribosomal peptide synthetases, and firefly luciferase. ACS Chem Biol. 2009; 4(10):811-27. PMC: 2769252. DOI: 10.1021/cb900156h. View

Reger A, Wu R, Dunaway-Mariano D, Gulick A . Structural characterization of a 140 degrees domain movement in the two-step reaction catalyzed by 4-chlorobenzoate:CoA ligase. Biochemistry. 2008; 47(31):8016-25. PMC: 2666193. DOI: 10.1021/bi800696y. View

Ingram-Smith C, Woods B, Smith K . Characterization of the acyl substrate binding pocket of acetyl-CoA synthetase. Biochemistry. 2006; 45(38):11482-90. DOI: 10.1021/bi061023e. View

Challis G, Ravel J, Townsend C . Predictive, structure-based model of amino acid recognition by nonribosomal peptide synthetase adenylation domains. Chem Biol. 2000; 7(3):211-24. DOI: 10.1016/s1074-5521(00)00091-0. View

Jogl G, Tong L . Crystal structure of yeast acetyl-coenzyme A synthetase in complex with AMP. Biochemistry. 2004; 43(6):1425-31. DOI: 10.1021/bi035911a. View

10.

Conti E, Stachelhaus T, Marahiel M, Brick P . Structural basis for the activation of phenylalanine in the non-ribosomal biosynthesis of gramicidin S. EMBO J. 1997; 16(14):4174-83. PMC: 1170043. DOI: 10.1093/emboj/16.14.4174. View

11.

Kochan G, Pilka E, von Delft F, Oppermann U, Yue W . Structural snapshots for the conformation-dependent catalysis by human medium-chain acyl-coenzyme A synthetase ACSM2A. J Mol Biol. 2009; 388(5):997-1008. DOI: 10.1016/j.jmb.2009.03.064. View

12.

Marahiel M, Stachelhaus T, Mootz H . Modular Peptide Synthetases Involved in Nonribosomal Peptide Synthesis. Chem Rev. 2002; 97(7):2651-2674. DOI: 10.1021/cr960029e. View

13.

Gulick A, Lu X, Dunaway-Mariano D . Crystal structure of 4-chlorobenzoate:CoA ligase/synthetase in the unliganded and aryl substrate-bound states. Biochemistry. 2004; 43(27):8670-9. DOI: 10.1021/bi049384m. View

14.

Wilson D, Aldrich C . A continuous kinetic assay for adenylation enzyme activity and inhibition. Anal Biochem. 2010; 404(1):56-63. PMC: 2900519. DOI: 10.1016/j.ab.2010.04.033. View

15.

Meng Y, Ingram-Smith C, Cooper L, Smith K . Characterization of an archaeal medium-chain acyl coenzyme A synthetase from Methanosarcina acetivorans. J Bacteriol. 2010; 192(22):5982-90. PMC: 2976453. DOI: 10.1128/JB.00600-10. View

16.

Stuible H, Buttner D, Ehlting J, Hahlbrock K, Kombrink E . Mutational analysis of 4-coumarate:CoA ligase identifies functionally important amino acids and verifies its close relationship to other adenylate-forming enzymes. FEBS Lett. 2000; 467(1):117-22. DOI: 10.1016/s0014-5793(00)01133-9. View

17.

Gulick A, Starai V, Horswill A, Homick K, Escalante-Semerena J . The 1.75 A crystal structure of acetyl-CoA synthetase bound to adenosine-5'-propylphosphate and coenzyme A. Biochemistry. 2003; 42(10):2866-73. DOI: 10.1021/bi0271603. View

18.

Yonus H, Neumann P, Zimmermann S, May J, Marahiel M, Stubbs M . Crystal structure of DltA. Implications for the reaction mechanism of non-ribosomal peptide synthetase adenylation domains. J Biol Chem. 2008; 283(47):32484-91. DOI: 10.1074/jbc.M800557200. View

19.

Pavela-Vrancic M, van Liempt H, Pfeifer E, Freist W, Von Dohren H . Nucleotide binding by multienzyme peptide synthetases. Eur J Biochem. 1994; 220(2):535-42. DOI: 10.1111/j.1432-1033.1994.tb18653.x. View

20.

Samanta S, Harwood C . Use of the Rhodopseudomonas palustris genome sequence to identify a single amino acid that contributes to the activity of a coenzyme A ligase with chlorinated substrates. Mol Microbiol. 2005; 55(4):1151-9. DOI: 10.1111/j.1365-2958.2004.04452.x. View