1jdw Citations

Crystal structure and mechanism of human L-arginine:glycine amidinotransferase: a mitochondrial enzyme involved in creatine biosynthesis.

EMBO J. 16 3373-85 (1997)
Related entries: 4jdw, 2jdw, 3jdw

Cited: 30 times
EuropePMC logo PMID: 9218780

Abstract

L-arginine:glycine amidinotransferase (AT) catalyses the committed step in creatine biosynthesis by formation of guanidinoacetic acid, the immediate precursor of creatine. We have determined the crystal structure of the recombinant human enzyme by multiple isomorphous replacement at 1.9 A resolution. A telluromethionine derivative was used in sequence assignment. The structure of AT reveals a new fold with 5-fold pseudosymmetry of circularly arranged betabeta alphabeta-modules. These enclose the active site compartment, which is accessible only through a narrow channel. The overall structure resembles a basket with handles that are formed from insertions into the betabeta alphabeta-modules. Binding of L-ornithine, a product inhibitor, reveals a marked induced-fit mechanism, with a loop at the active site entrance changing its conformation accompanied by a shift of an alpha-helix by -4 A. Binding of the arginine educt to the inactive mutant C407A shows a similar mode of binding. A reaction mechanism with a catalytic triad Cys-His-Asp is proposed on the basis of substrate and product bound states.

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Reviews citing this publication (4)

  1. Creatine biosynthesis and transport in health and disease. Joncquel-Chevalier Curt M, Voicu PM, Fontaine M, Dessein AF, Porchet N, Mention-Mulliez K, Dobbelaere D, Soto-Ares G, Cheillan D, Vamecq J. Biochimie 119 146-165 (2015)
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  3. Novel sequences propel familiar folds. Jawad Z, Paoli M. Structure 10 447-454 (2002)
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  2. The CATH classification revisited--architectures reviewed and new ways to characterize structural divergence in superfamilies. Cuff AL, Sillitoe I, Lewis T, Redfern OC, Garratt R, Thornton J, Orengo CA. Nucleic Acids Res. 37 D310-4 (2009)
  3. Structural basis for histone N-terminal recognition by human peptidylarginine deiminase 4. Arita K, Shimizu T, Hashimoto H, Hidaka Y, Yamada M, Sato M. Proc. Natl. Acad. Sci. U.S.A. 103 5291-5296 (2006)
  4. Inhibition of PAD4 activity is sufficient to disrupt mouse and human NET formation. Lewis HD, Liddle J, Coote JE, Atkinson SJ, Barker MD, Bax BD, Bicker KL, Bingham RP, Campbell M, Chen YH, Chung CW, Craggs PD, Davis RP, Eberhard D, Joberty G, Lind KE, Locke K, Maller C, Martinod K, Patten C, Polyakova O, Rise CE, Rüdiger M, Sheppard RJ, Slade DJ, Thomas P, Thorpe J, Yao G, Drewes G, Wagner DD, Thompson PR, Prinjha RK, Wilson DM. Nat. Chem. Biol. 11 189-191 (2015)
  5. A novel superfamily of enzymes that catalyze the modification of guanidino groups. Shirai H, Blundell TL, Mizuguchi K. Trends Biochem. Sci. 26 465-468 (2001)
  6. Crystal structures of arginine deiminase with covalent reaction intermediates; implications for catalytic mechanism. Das K, Butler GH, Kwiatkowski V, Clark AD, Yadav P, Arnold E. Structure 12 657-667 (2004)
  7. A novel gene encoding amidinotransferase in the cylindrospermopsin producing cyanobacterium Aphanizomenon ovalisporum. Shalev-Alon G, Sukenik A, Livnah O, Schwarz R, Kaplan A. FEMS Microbiol. Lett. 209 87-91 (2002)
  8. Bioincorporation of telluromethionine into proteins: a promising new approach for X-ray structure analysis of proteins. Budisa N, Karnbrock W, Steinbacher S, Humm A, Prade L, Neuefeind T, Moroder L, Huber R. J. Mol. Biol. 270 616-623 (1997)
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  10. Isolation and characterization of the gene coding for the amidinotransferase involved in the biosynthesis of phaseolotoxin in Pseudomonas syringae pv. phaseolicola. Hernández-Guzmán G, Alvarez-Morales A. Mol. Plant Microbe Interact. 14 545-554 (2001)
  11. Structure of the mammalian NOS regulator dimethylarginine dimethylaminohydrolase: A basis for the design of specific inhibitors. Frey D, Braun O, Briand C, Vasák M, Grütter MG. Structure 14 901-911 (2006)
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  13. Novel pathways in the pathobiology of human abdominal aortic aneurysms. Hinterseher I, Erdman R, Elmore JR, Stahl E, Pahl MC, Derr K, Golden A, Lillvis JH, Cindric MC, Jackson K, Bowen WD, Schworer CM, Chernousov MA, Franklin DP, Gray JL, Garvin RP, Gatalica Z, Carey DJ, Tromp G, Kuivaniemi H. Pathobiology 80 1-10 (2013)
  14. Research Support, Non-U.S. Gov't Homoarginine, arginine, and relatives: analysis, metabolism, transport, physiology, and pathology. Tsikas D, Wu G. Amino Acids 47 1697-1702 (2015)
  15. Biosynthesis of homoarginine (hArg) and asymmetric dimethylarginine (ADMA) from acutely and chronically administered free L-arginine in humans. Kayacelebi AA, Langen J, Weigt-Usinger K, Chobanyan-Jürgens K, Mariotti F, Schneider JY, Rothmann S, Frölich JC, Atzler D, Choe CU, Schwedhelm E, Huneau JF, Lücke T, Tsikas D. Amino Acids 47 1893-1908 (2015)
  16. Phytochelatin synthase, papain's cousin, in stereo. Rea PA. Proc. Natl. Acad. Sci. U.S.A. 103 507-508 (2006)
  17. Molecular insights into the biosynthesis of guadinomine: a type III secretion system inhibitor. Holmes TC, May AE, Zaleta-Rivera K, Ruby JG, Skewes-Cox P, Fischbach MA, DeRisi JL, Iwatsuki M, Ōmura S, Khosla C. J. Am. Chem. Soc. 134 17797-17806 (2012)
  18. Insight into the catalytic mechanism of arginine deiminase: functional studies on the crucial sites. Wei Y, Zhou H, Sun Y, He Y, Luo Y. Proteins 66 740-750 (2007)
  19. Specific reactions of S-nitrosothiols with cysteine hydrolases: A comparative study between dimethylargininase-1 and CTP synthetase. Braun O, Knipp M, Chesnov S, Vasák M. Protein Sci. 16 1522-1534 (2007)
  20. Characterization and manipulation of the Pseudomonas aeruginosa dimethylarginine dimethylaminohydrolase monomer--dimer equilibrium. Plevin MJ, Magalhães BS, Harris R, Sankar A, Perkins SJ, Driscoll PC. J. Mol. Biol. 341 171-184 (2004)
  21. Substrate binding and catalysis by L-arginine:glycine amidinotransferase--a mutagenesis and crystallographic study. Fritsche E, Humm A, Huber R. Eur. J. Biochem. 247 483-490 (1997)


Related citations provided by authors (4)

  1. Structure and Reaction Mechanism of L-Arginine:Glycine Amidinotransferase. Humm A, Fritsche E, Steinbacher S Biol. Chem. Hoppe-Seyler 378 193- (1997)
  2. Substrate Binding and Catalysis by L-Arginine:Glycine Amidinotransferase--A Mutagenesis and Crystallographic Study. Fritsche E, Humm A, Huber R Eur. J. Biochem. 247 483- (1997)
  3. Recombinant Expression and Isolation of Human L-Arginine:Glycine Amidinotransferase and Identification of its Active-Site Cysteine Residue. Humm A, Fritsche E, Mann K, Gohl M, Huber R Biochem. J. 322 771- (1997)
  4. Bioincorporation of Telluromethionine Into Proteins: A Promising New Approach for X-Ray Structure Analysis of Proteins. Budisa N, Karnbrock W, Steinbacher S, Humm A, Prade L, Neuefeind T, Moroder L, Huber R J. Mol. Biol. 270 616- (1997)