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Identification of the citrate-binding site of human ATP-citrate lyase using X-ray crystallography.

Sun T, Hayakawa K, Bateman KS, Fraser ME
J Biol Chem 285 27418-27428 (2010)
Cited: 41 times
EuropePMC logo PMID: 20558738

Abstract

ATP-citrate lyase (ACLY) catalyzes the conversion of citrate and CoA into acetyl-CoA and oxaloacetate, coupled with the hydrolysis of ATP. In humans, ACLY is the cytoplasmic enzyme linking energy metabolism from carbohydrates to the production of fatty acids. In situ proteolysis of full-length human ACLY gave crystals of a truncated form, revealing the conformations of residues 2-425, 487-750, and 767-820 of the 1101-amino acid protein. Residues 2-425 form three domains homologous to the beta-subunit of succinyl-CoA synthetase (SCS), while residues 487-820 form two domains homologous to the alpha-subunit of SCS. The crystals were grown in the presence of tartrate or the substrate, citrate, and the structure revealed the citrate-binding site. A loop formed by residues 343-348 interacts via specific hydrogen bonds with the hydroxyl and carboxyl groups on the prochiral center of citrate. Arg-379 forms a salt bridge with the pro-R carboxylate of citrate. The pro-S carboxylate is free to react, providing insight into the stereospecificity of ACLY. Because this is the first structure of any member of the acyl-CoA synthetase (NDP-forming) superfamily in complex with its organic acid substrate, locating the citrate-binding site is significant for understanding the catalytic mechanism of each member, including the prototype SCS. Comparison of the CoA-binding site of SCSs with the similar structure in ACLY showed that ACLY possesses a different CoA-binding site. Comparisons of the nucleotide-binding site of SCSs with the similar structure in ACLY indicates that this is the ATP-binding site of ACLY.

Articles - 3mwe mentioned but not cited (3)

  1. Identification of the citrate-binding site of human ATP-citrate lyase using X-ray crystallography. Sun T, Hayakawa K, Bateman KS, Fraser ME. J. Biol. Chem. 285 27418-27428 (2010)
  2. ADP-Mg2+ bound to the ATP-grasp domain of ATP-citrate lyase. Sun T, Hayakawa K, Fraser ME. Acta Crystallogr. Sect. F Struct. Biol. Cryst. Commun. 67 1168-1172 (2011)
  3. CARDIO-PRED: an in silico tool for predicting cardiovascular-disorder associated proteins. Jain P, Thukral N, Gahlot LK, Hasija Y. Syst Synth Biol 9 55-66 (2015)


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  1. Adenosine triphosphate citrate lyase: Emerging target in the treatment of dyslipidemia. Lemus HN, Mendivil CO. J Clin Lipidol 9 384-389 (2015)
  2. Fatty Acids and Breast Cancer: Make Them on Site or Have Them Delivered. Kinlaw WB, Baures PW, Lupien LE, Davis WL, Kuemmerle NB. J. Cell. Physiol. 231 2128-2141 (2016)
  3. The vital role of ATP citrate lyase in chronic diseases. Khwairakpam AD, Banik K, Girisa S, Shabnam B, Shakibaei M, Fan L, Arfuso F, Monisha J, Wang H, Mao X, Sethi G, Kunnumakkara AB. J Mol Med (Berl) 98 71-95 (2020)
  4. A comprehensive review of long non-coding RNAs in the pathogenesis and development of non-alcoholic fatty liver disease. Shabgah AG, Norouzi F, Hedayati-Moghadam M, Soleimani D, Pahlavani N, Navashenaq JG. Nutr Metab (Lond) 18 22 (2021)
  5. Liver glucose metabolism in humans. Adeva-Andany MM, Pérez-Felpete N, Fernández-Fernández C, Donapetry-García C, Pazos-García C. Biosci. Rep. 36 (2016)
  6. Mechanisms of AMPK in the maintenance of ATP balance during energy metabolism. Ke R, Xu Q, Li C, Luo L, Huang D. Cell Biol. Int. 42 384-392 (2018)
  7. Interactions between inorganic and organic phases in bone tissue as a source of inspiration for design of novel nanocomposites. Farbod K, Nejadnik MR, Jansen JA, Leeuwenburgh SC. Tissue Eng Part B Rev 20 173-188 (2014)
  8. Fatty acid metabolism reprogramming in ccRCC: mechanisms and potential targets. Tan SK, Hougen HY, Merchan JR, Gonzalgo ML, Welford SM. Nat Rev Urol 20 48-60 (2023)

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  1. The lipogenesis pathway as a cancer target. Abramson HN. J. Med. Chem. 54 5615-5638 (2011)
  2. Structure of ATP citrate lyase and the origin of citrate synthase in the Krebs cycle. Verschueren KHG, Blanchet C, Felix J, Dansercoer A, De Vos D, Bloch Y, Van Beeumen J, Svergun D, Gutsche I, Savvides SN, Verstraete K. Nature 568 571-575 (2019)
  3. An allosteric mechanism for potent inhibition of human ATP-citrate lyase. Wei J, Leit S, Kuai J, Therrien E, Rafi S, Harwood HJ, DeLaBarre B, Tong L. Nature 568 566-570 (2019)
  4. Carbon metabolic pathways in phototrophic bacteria and their broader evolutionary implications. Tang KH, Tang YJ, Blankenship RE. Front Microbiol 2 165 (2011)
  5. Srebp-controlled glucose metabolism is essential for NK cell functional responses. Assmann N, O'Brien KL, Donnelly RP, Dyck L, Zaiatz-Bittencourt V, Loftus RM, Heinrich P, Oefner PJ, Lynch L, Gardiner CM, Dettmer K, Finlay DK. Nat. Immunol. 18 1197-1206 (2017)
  6. LC-MS proteomics analysis of the insulin/IGF-1-deficient Caenorhabditis elegans daf-2(e1370) mutant reveals extensive restructuring of intermediary metabolism. Depuydt G, Xie F, Petyuk VA, Smolders A, Brewer HM, Camp DG, Smith RD, Braeckman BP. J. Proteome Res. 13 1938-1956 (2014)
  7. Rotenone induces reductive stress and triacylglycerol deposition in C2C12 cells. He Q, Wang M, Petucci C, Gardell SJ, Han X. Int. J. Biochem. Cell Biol. 45 2749-2755 (2013)
  8. A defect in ATP-citrate lyase links acetyl-CoA production, virulence factor elaboration and virulence in Cryptococcus neoformans. Griffiths EJ, Hu G, Fries B, Caza M, Wang J, Gsponer J, Gates-Hollingsworth MA, Kozel TR, De Repentigny L, Kronstad JW. Mol. Microbiol. 86 1404-1423 (2012)
  9. Cytosolic functions of MORC2 in lipogenesis and adipogenesis. Sánchez-Solana B, Li DQ, Kumar R. Biochim. Biophys. Acta 1843 316-326 (2014)
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  13. Molecular basis for acetyl-CoA production by ATP-citrate lyase. Wei X, Schultz K, Bazilevsky GA, Vogt A, Marmorstein R. Nat Struct Mol Biol 27 33-41 (2020)
  14. Structure of NDP-forming Acetyl-CoA synthetase ACD1 reveals a large rearrangement for phosphoryl transfer. Weiße RH, Faust A, Schmidt M, Schönheit P, Scheidig AJ. Proc. Natl. Acad. Sci. U.S.A. 113 E519-28 (2016)
  15. ATP-citrate lyase multimerization is required for coenzyme-A substrate binding and catalysis. Bazilevsky GA, Affronti HC, Wei X, Campbell SL, Wellen KE, Marmorstein R. J Biol Chem 294 7259-7268 (2019)
  16. Binding of hydroxycitrate to human ATP-citrate lyase. Hu J, Komakula A, Fraser ME. Acta Crystallogr D Struct Biol 73 660-671 (2017)
  17. Cellular citrate levels establish a regulatory link between energy metabolism and the hepatic iron hormone hepcidin. da Silva AR, Neves J, Mleczko-Sanecka K, Tandon A, Sauer SW, Hentze MW, Muckenthaler MU. J. Mol. Med. 95 851-860 (2017)
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  19. Discovery of furan carboxylate derivatives as novel inhibitors of ATP-citrate lyase via virtual high-throughput screening. Jernigan FE, Hanai JI, Sukhatme VP, Sun L. Bioorg. Med. Chem. Lett. 27 929-935 (2017)
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  21. Identification of the active site residues in ATP-citrate lyase's carboxy-terminal portion. Nguyen VH, Singh N, Medina A, Usón I, Fraser ME. Protein Sci 28 1840-1849 (2019)
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  25. Caspase-10 inhibits ATP-citrate lyase-mediated metabolic and epigenetic reprogramming to suppress tumorigenesis. Kumari R, Deshmukh RS, Das S. Nat Commun 10 4255 (2019)
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  29. Molecular cloning and characterization of the ATP citrate lyase from carotenogenic yeast Phaffia rhodozyma. Chávez-Cabrera C, Marsch R, Bartolo-Aguilar Y, Flores-Bustamante ZR, Hidalgo-Lara ME, Martínez-Cárdenas A, Cancino-Díaz JC, Sánchez S, Flores-Cotera LB. FEMS Yeast Res. 15 (2015)
  30. The structure of succinyl-CoA synthetase bound to the succinyl-phosphate intermediate clarifies the catalytic mechanism of ATP-citrate lyase. Huang J, Fraser ME. Acta Crystallogr F Struct Biol Commun 78 363-370 (2022)


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