PDBsum entry 1jdw

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Transferase PDB id
Protein chain
360 a.a. *
Waters ×588
* Residue conservation analysis
PDB id:
Name: Transferase
Title: Crystal structure and mechanism of l-arginine: glycine amidinotransferase: a mitochondrial enzyme involved in creatine biosynthesis
Structure: L-arginine\:glycine amidinotransferase. Chain: a. Fragment: residues 64 - 423. Synonym: transamidinase, at38. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Cell_line: bl21. Organ: kidney. Organelle: mitochondria. Cellular_location: intermembrane space of mitochondria and cytoplasm. Gene: at38h.
Biol. unit: Homo-Dimer (from PDB file)
1.90Å     R-factor:   0.196     R-free:   0.231
Authors: A.Humm,E.Fritsche,S.Steinbacher,R.Huber
Key ref:
A.Humm et al. (1997). Crystal structure and mechanism of human L-arginine:glycine amidinotransferase: a mitochondrial enzyme involved in creatine biosynthesis. EMBO J, 16, 3373-3385. PubMed id: 9218780 DOI: 10.1093/emboj/16.12.3373
22-Jan-97     Release date:   28-Jan-98    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
P50440  (GATM_HUMAN) -  Glycine amidinotransferase, mitochondrial
423 a.a.
360 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.  - Glycine amidinotransferase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]

Creatine Biosynthesis
      Reaction: L-arginine + glycine = L-ornithine + guanidinoacetate
Bound ligand (Het Group name = BME)
matches with 50.00% similarity
= L-ornithine
+ guanidinoacetate
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     membrane   6 terms 
  Biological process     small molecule metabolic process   11 terms 
  Biochemical function     transferase activity     4 terms  


DOI no: 10.1093/emboj/16.12.3373 EMBO J 16:3373-3385 (1997)
PubMed id: 9218780  
Crystal structure and mechanism of human L-arginine:glycine amidinotransferase: a mitochondrial enzyme involved in creatine biosynthesis.
A.Humm, E.Fritsche, S.Steinbacher, R.Huber.
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.
  Selected figure(s)  
Figure 3.
Figure 3 Representation of the individual modules of the AT structure. The figure was made with MOLSCRIPT (Kraulis, 1991), the colours are the same as in Figure 2A.
Figure 10.
Figure 10 Superposition of a 2F[o]-F[c] electron density from AT at a resolution of 1.9 , contoured at 1 (blue), with an F[o]-F[c] electron difference density of AT, expressed with N-acetyltelluromethionine, at a resolution of 3.0 , contoured at 5 (red). The image displays the positions of three tellurium atoms revealing the methionine residues. The figure was produced using FRODO (Jones, 1978).
  The above figures are reprinted from an Open Access publication published by Macmillan Publishers Ltd: EMBO J (1997, 16, 3373-3385) copyright 1997.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21308988 N.Longo, O.Ardon, R.Vanzo, E.Schwartz, and M.Pasquali (2011).
Disorders of creatine transport and metabolism.
  Am J Med Genet C Semin Med Genet, 157, 72-78.  
18996897 A.L.Cuff, I.Sillitoe, T.Lewis, O.C.Redfern, R.Garratt, J.Thornton, and C.A.Orengo (2009).
The CATH classification revisited--architectures reviewed and new ways to characterize structural divergence in superfamilies.
  Nucleic Acids Res, 37, D310-D314.  
18482699 T.W.Linsky, A.F.Monzingo, E.M.Stone, J.D.Robertus, and W.Fast (2008).
Promiscuous partitioning of a covalent intermediate common in the pentein superfamily.
  Chem Biol, 15, 467-475.
PDB code: 3bpb
17202790 H.Shirai, and M.Kobori (2007).
[Interface between bioinformatics and docking study]
  Yakugaku Zasshi, 127, 103-112.  
17600152 O.Braun, M.Knipp, S.Chesnov, and M.Vasák (2007).
Specific reactions of S-nitrosothiols with cysteine hydrolases: A comparative study between dimethylargininase-1 and CTP synthetase.
  Protein Sci, 16, 1522-1534.  
17080455 Y.Wei, H.Zhou, Y.Sun, Y.He, and Y.Luo (2007).
Insight into the catalytic mechanism of arginine deiminase: functional studies on the crucial sites.
  Proteins, 66, 740-750.  
16698551 D.Frey, O.Braun, C.Briand, M.Vasák, and M.G.Grütter (2006).
Structure of the mammalian NOS regulator dimethylarginine dimethylaminohydrolase: A basis for the design of specific inhibitors.
  Structure, 14, 901-911.
PDB codes: 2c6z 2ci1 2ci3 2ci4 2ci5 2ci6 2ci7
16779844 H.Shirai, Y.Mokrab, and K.Mizuguchi (2006).
The guanidino-group modifying enzymes: structural basis for their diversity and commonality.
  Proteins, 64, 1010-1023.  
16567635 K.Arita, T.Shimizu, H.Hashimoto, Y.Hidaka, M.Yamada, and M.Sato (2006).
Structural basis for histone N-terminal recognition by human peptidylarginine deiminase 4.
  Proc Natl Acad Sci U S A, 103, 5291-5296.
PDB codes: 2dew 2dex 2dey
16407124 P.A.Rea (2006).
Phytochelatin synthase, papain's cousin, in stereo.
  Proc Natl Acad Sci U S A, 103, 507-508.  
16091358 A.Galkin, X.Lu, D.Dunaway-Mariano, and O.Herzberg (2005).
Crystal structures representing the Michaelis complex and the thiouronium reaction intermediate of Pseudomonas aeruginosa arginine deiminase.
  J Biol Chem, 280, 34080-34087.
PDB codes: 2a9g 2aaf 2abr 2aci
15703173 A.Tocilj, J.D.Schrag, Y.Li, B.L.Schneider, L.Reitzer, A.Matte, and M.Cygler (2005).
Crystal structure of N-succinylarginine dihydrolase AstB, bound to substrate and product, an enzyme from the arginine catabolic pathway of Escherichia coli.
  J Biol Chem, 280, 15800-15808.
PDB codes: 1ynf 1ynh 1yni
14701825 A.Galkin, L.Kulakova, E.Sarikaya, K.Lim, A.Howard, and O.Herzberg (2004).
Structural insight into arginine degradation by arginine deiminase, an antibacterial and parasite drug target.
  J Biol Chem, 279, 14001-14008.
PDB code: 1rxx
15247907 K.Arita, H.Hashimoto, T.Shimizu, K.Nakashima, M.Yamada, and M.Sato (2004).
Structural basis for Ca(2+)-induced activation of human PAD4.
  Nat Struct Mol Biol, 11, 777-783.
PDB codes: 1wd8 1wd9 1wda
15062088 K.Das, G.H.Butler, V.Kwiatkowski, A.D.Clark, P.Yadav, and E.Arnold (2004).
Crystal structures of arginine deiminase with covalent reaction intermediates; implications for catalytic mechanism.
  Structure, 12, 657-667.
PDB codes: 1lxy 1s9r
15004013 O.K.Vatamaniuk, S.Mari, A.Lang, S.Chalasani, L.O.Demkiv, and P.A.Rea (2004).
Phytochelatin synthase, a dipeptidyltransferase that undergoes multisite acylation with gamma-glutamylcysteine during catalysis: stoichiometric and site-directed mutagenic analysis of arabidopsis thaliana PCS1-catalyzed phytochelatin synthesis.
  J Biol Chem, 279, 22449-22460.  
12441345 M.Knipp, O.Braun, P.M.Gehrig, R.Sack, and M.Vasák (2003).
Zn(II)-free dimethylargininase-1 (DDAH-1) is inhibited upon specific Cys-S-nitrosylation.
  J Biol Chem, 278, 3410-3416.  
12007659 G.Shalev-Alon, A.Sukenik, O.Livnah, R.Schwarz, and A.Kaplan (2002).
A novel gene encoding amidinotransferase in the cylindrospermopsin producing cyanobacterium Aphanizomenon ovalisporum.
  FEMS Microbiol Lett, 209, 87-91.  
11937049 Z.Jawad, and M.Paoli (2002).
Novel sequences propel familiar folds.
  Structure, 10, 447-454.  
11310742 G.Hernández-Guzmán, and A.Alvarez-Morales (2001).
Isolation and characterization of the gene coding for the amidinotransferase involved in the biosynthesis of phaseolotoxin in Pseudomonas syringae pv. phaseolicola.
  Mol Plant Microbe Interact, 14, 545-554.  
11504612 H.Shirai, T.L.Blundell, and K.Mizuguchi (2001).
A novel superfamily of enzymes that catalyze the modification of guanidino groups.
  Trends Biochem Sci, 26, 465-468.  
11685232 O.Lichtarge (2001).
Getting past appearances: the many-fold consequences of remote homology.
  Nat Struct Biol, 8, 918-920.  
11406387 S.A.Teichmann, A.G.Murzin, and C.Chothia (2001).
Determination of protein function, evolution and interactions by structural genomics.
  Curr Opin Struct Biol, 11, 354-363.  
9915841 E.Fritsche, A.Humm, and R.Huber (1999).
The ligand-induced structural changes of human L-Arginine:Glycine amidinotransferase. A mutational and crystallographic study.
  J Biol Chem, 274, 3026-3032.
PDB codes: 1jdx 2jdx 5jdw 6jdw 7jdw 8jdw 9jdw
9266688 E.Fritsche, A.Humm, and R.Huber (1997).
Substrate binding and catalysis by L-arginine:glycine amidinotransferase--a mutagenesis and crystallographic study.
  Eur J Biochem, 247, 483-490.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB code is shown on the right.