PDBsum entry 1gsj

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Kinase PDB id
Protein chain
258 a.a. *
Waters ×198
* Residue conservation analysis
PDB id:
Name: Kinase
Title: Selenomethionine substituted n-acetyl-l-glutamate kinase from escherichia coli complexed with its substrate n-acetyl-l-glutamate and its substrate analog amppnp
Structure: Acetylglutamate kinase. Chain: a. Engineered: yes. Other_details: selenomethionine substituted enzyme
Source: Escherichia coli. Organism_taxid: 562. Strain: bl21 (de3). Expressed in: escherichia coli. Expression_system_taxid: 562. Other_details: from novagen
Biol. unit: Dimer (from PDB file)
1.85Å     R-factor:   0.198     R-free:   0.226
Authors: S.Ramon-Maiques,A.Marina,F.Gil-Ortiz,I.Fita,V.Rubio
Key ref:
S.Ramón-Maiques et al. (2002). Structure of acetylglutamate kinase, a key enzyme for arginine biosynthesis and a prototype for the amino acid kinase enzyme family, during catalysis. Structure, 10, 329-342. PubMed id: 12005432 DOI: 10.1016/S0969-2126(02)00721-9
07-Jan-02     Release date:   16-May-02    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
P0A6C8  (ARGB_ECOLI) -  Acetylglutamate kinase
258 a.a.
258 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.  - Acetylglutamate kinase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]

Ornithine Biosynthesis
      Reaction: ATP + N-acetyl-L-glutamate = ADP + N-acetyl-L-glutamate 5-phosphate
Bound ligand (Het Group name = NLG)
corresponds exactly
Bound ligand (Het Group name = ANP)
matches with 81.00% similarity
+ N-acetyl-L-glutamate 5-phosphate
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     cytoplasm   1 term 
  Biological process     response to DNA damage stimulus   4 terms 
  Biochemical function     nucleotide binding     5 terms  


DOI no: 10.1016/S0969-2126(02)00721-9 Structure 10:329-342 (2002)
PubMed id: 12005432  
Structure of acetylglutamate kinase, a key enzyme for arginine biosynthesis and a prototype for the amino acid kinase enzyme family, during catalysis.
S.Ramón-Maiques, A.Marina, F.Gil-Ortiz, I.Fita, V.Rubio.
N-Acetyl-L-glutamate kinase (NAGK), a member of the amino acid kinase family, catalyzes the second and frequently controlling step of arginine synthesis. The Escherichia coli NAGK crystal structure to 1.5 A resolution reveals a 258-residue subunit homodimer nucleated by a central 16-stranded molecular open beta sheet sandwiched between alpha helices. In each subunit, AMPPNP, as an alphabetagamma-phosphate-Mg2+ complex, binds along the sheet C edge, and N-acetyl-L-glutamate binds near the dyadic axis with its gamma-COO- aligned at short distance from the gamma-phosphoryl, indicating associative phosphoryl transfer assisted by: (1) Mg2+ complexation; (2) the positive charges on Lys8, Lys217, and on two helix dipoles; and (3) by hydrogen bonding with the y-phosphate. The structural resemblance with carbamate kinase and the alignment of the sequences suggest that NAGK is a structural and functional prototype for the amino acid kinase family, which differs from other acylphosphate-making devices represented by phosphoglycerate kinase, acetate kinase, and biotin carboxylase.
  Selected figure(s)  
Figure 5.
Figure 5. 2F[obs] -F[calc] Density Map and Model of MgAMPPNP and NAG Bound to the Enzyme, and Comparison with ADP Binding by CK-like CPS(A) 2F[obs] -F[calc] density map contoured at 0.8 s for bound MgAMPPNP (including, in light blue, two water molecules coordinated to Mg) and NAG. Helices B and E and the side chains of lysines 8, 61, and 217 are shown. Drawn with BOBSCRIPT [60].(B) Stereoview of bond representation of bound MgAMPPNP, NAG, and nearby NAGK groups (in black) superimposed with bound ADP and nearby groups in CK-like CPS from Pyrococcus furiosus (in red; Protein Data Bank accession number 1e19).
  The above figure is reprinted by permission from Cell Press: Structure (2002, 10, 329-342) copyright 2002.  
  Figure was selected by the author.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20386738 E.Marcos, R.Crehuet, and I.Bahar (2010).
On the conservation of the slow conformational dynamics within the amino acid kinase family: NAGK the paradigm.
  PLoS Comput Biol, 6, e1000738.  
  20091669 I.Pérez-Arellano, F.Carmona-Alvarez, A.I.Martínez, J.Rodríguez-Díaz, and J.Cervera (2010).
Pyrroline-5-carboxylate synthase and proline biosynthesis: from osmotolerance to rare metabolic disease.
  Protein Sci, 19, 372-382.  
20544237 I.Pérez-Arellano, and J.Cervera (2010).
Glutamate kinase from Thermotoga maritima: characterization of a thermophilic enzyme for proline biosynthesis.
  Extremophiles, 14, 409-415.  
20303810 L.Caldovic, N.Ah Mew, D.Shi, H.Morizono, M.Yudkoff, and M.Tuchman (2010).
N-acetylglutamate synthase: structure, function and defects.
  Mol Genet Metab, 100, S13-S19.  
  20392112 N.Dellas, and J.P.Noel (2010).
Mutation of archaeal isopentenyl phosphate kinase highlights mechanism and guides phosphorylation of additional isoprenoid monophosphates.
  ACS Chem Biol, 5, 589-601.
PDB codes: 3k4o 3k4y 3k52 3k56
19095660 L.Min, Z.Jin, L.Caldovic, H.Morizono, N.M.Allewell, M.Tuchman, and D.Shi (2009).
Mechanism of Allosteric Inhibition of N-Acetyl-L-glutamate Synthase by L-Arginine.
  J Biol Chem, 284, 4873-4880.
PDB codes: 3d2m 3d2p
18184660 D.Shi, V.Sagar, Z.Jin, X.Yu, L.Caldovic, H.Morizono, N.M.Allewell, and M.Tuchman (2008).
The crystal structure of N-acetyl-L-glutamate synthase from Neisseria gonorrhoeae provides insights into mechanisms of catalysis and regulation.
  J Biol Chem, 283, 7176-7184.
PDB codes: 2r8v 2r98 3b8g
18802692 H.Takagi (2008).
Proline as a stress protectant in yeast: physiological functions, metabolic regulations, and biotechnological applications.
  Appl Microbiol Biotechnol, 81, 211-223.  
19013524 J.L.Llácer, I.Fita, and V.Rubio (2008).
Arginine and nitrogen storage.
  Curr Opin Struct Biol, 18, 673-681.  
18263723 M.L.Fernández-Murga, and V.Rubio (2008).
Basis of arginine sensitivity of microbial N-acetyl-L-glutamate kinases: mutagenesis and protein engineering study with the Pseudomonas aeruginosa and Escherichia coli enzymes.
  J Bacteriol, 190, 3018-3025.  
18801197 N.Haskins, M.Panglao, Q.Qu, H.Majumdar, J.Cabrera-Luque, H.Morizono, M.Tuchman, and L.Caldovic (2008).
Inversion of allosteric effect of arginine on N-acetylglutamate synthase, a molecular marker for evolution of tetrapods.
  BMC Biochem, 9, 24.  
18701452 S.Pakhomova, S.G.Bartlett, A.Augustus, T.Kuzuyama, and M.E.Newcomer (2008).
Crystal Structure of Fosfomycin Resistance Kinase FomA from Streptomyces wedmorensis.
  J Biol Chem, 283, 28518-28526.
PDB codes: 3d40 3d41
17210578 C.Evrin, M.Straut, N.Slavova-Azmanova, N.Bucurenci, A.Onu, L.Assairi, M.Ionescu, N.Palibroda, O.Bârzu, and A.M.Gilles (2007).
Regulatory mechanisms differ in UMP kinases from gram-negative and gram-positive bacteria.
  J Biol Chem, 282, 7242-7253.  
17803682 I.Pérez-Arellano, J.Gallego, and J.Cervera (2007).
The PUA domain - a structural and functional overview.
  FEBS J, 274, 4972-4984.  
17425781 Q.Qu, H.Morizono, D.Shi, M.Tuchman, and L.Caldovic (2007).
A novel bifunctional N-acetylglutamate synthase-kinase from Xanthomonas campestris that is closely related to mammalian N-acetylglutamate synthase.
  BMC Biochem, 8, 4.  
17449694 T.Sekine, A.Kawaguchi, Y.Hamano, and H.Takagi (2007).
Desensitization of feedback inhibition of the Saccharomyces cerevisiae gamma-glutamyl kinase enhances proline accumulation and freezing tolerance.
  Appl Environ Microbiol, 73, 4011-4019.  
17913711 Y.Mizuno, G.B.Moorhead, and K.K.Ng (2007).
Structural basis for the regulation of N-acetylglutamate kinase by PII in Arabidopsis thaliana.
  J Biol Chem, 282, 35733-35740.
PDB code: 2rd5
17347518 Y.Xu, B.Labedan, and N.Glansdorff (2007).
Surprising arginine biosynthesis: a reappraisal of the enzymology and evolution of the pathway in microorganisms.
  Microbiol Mol Biol Rev, 71, 36-47.  
  17142901 D.Shi, L.Caldovic, Z.Jin, X.Yu, Q.Qu, L.Roth, H.Morizono, Y.Hathout, N.M.Allewell, and M.Tuchman (2006).
Expression, crystallization and preliminary crystallographic studies of a novel bifunctional N-acetylglutamate synthase/kinase from Xanthomonas campestris homologous to vertebrate N-acetylglutamate synthase.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 62, 1218-1222.  
16905770 M.Kotaka, J.Ren, M.Lockyer, A.R.Hawkins, and D.K.Stammers (2006).
Structures of R- and T-state Escherichia coli aspartokinase III. Mechanisms of the allosteric transition and inhibition by lysine.
  J Biol Chem, 281, 31544-31552.
PDB codes: 2j0w 2j0x
16409639 Y.Xu, N.Glansdorff, and B.Labedan (2006).
Bioinformatic analysis of an unusual gene-enzyme relationship in the arginine biosynthetic pathway among marine gamma proteobacteria: implications concerning the formation of N-acetylated intermediates in prokaryotes.
  BMC Genomics, 7, 4.  
15906321 A.J.Bordner, and R.Abagyan (2005).
Statistical analysis and prediction of protein-protein interfaces.
  Proteins, 60, 353-366.  
15857829 P.Briozzo, C.Evrin, P.Meyer, L.Assairi, N.Joly, O.Barzu, and A.M.Gilles (2005).
Structure of Escherichia coli UMP kinase differs from that of other nucleoside monophosphate kinases and sheds new light on enzyme regulation.
  J Biol Chem, 280, 25533-25540.
PDB codes: 2bnd 2bne 2bnf
15165234 A.Heinrich, M.Maheswaran, U.Ruppert, and K.Forchhammer (2004).
The Synechococcus elongatus P signal transduction protein controls arginine synthesis by complex formation with N-acetyl-L-glutamate kinase.
  Mol Microbiol, 52, 1303-1314.  
15050968 H.Morizono, L.Caldovic, D.Shi, and M.Tuchman (2004).
Mammalian N-acetylglutamate synthase.
  Mol Genet Metab, 81, S4-11.  
15502337 I.Pérez-Arellano, F.Gil-Ortiz, J.Cervera, and V.Rubio (2004).
Glutamate-5-kinase from Escherichia coli: gene cloning, overexpression, purification and crystallization of the recombinant enzyme and preliminary X-ray studies.
  Acta Crystallogr D Biol Crystallogr, 60, 2091-2094.  
15502156 M.Maheswaran, C.Urbanke, and K.Forchhammer (2004).
Complex formation and catalytic activation by the PII signaling protein of N-acetyl-L-glutamate kinase from Synechococcus elongatus strain PCC 7942.
  J Biol Chem, 279, 55202-55210.  
15150219 S.Burillo, I.Luque, I.Fuentes, and A.Contreras (2004).
Interactions between the nitrogen signal transduction protein PII and N-acetyl glutamate kinase in organisms that perform oxygenic photosynthesis.
  J Bacteriol, 186, 3346-3354.  
12869195 C.Gagyi, N.Bucurenci, O.Sîrbu, G.Labesse, M.Ionescu, A.Ofiteru, L.Assairi, S.Landais, A.Danchin, O.Bârzu, and A.M.Gilles (2003).
UMP kinase from the Gram-positive bacterium Bacillus subtilis is strongly dependent on GTP for optimal activity.
  Eur J Biochem, 270, 3196-3204.  
12603335 K.Pauwels, A.Abadjieva, P.Hilven, A.Stankiewicz, and M.Crabeel (2003).
The N-acetylglutamate synthase/N-acetylglutamate kinase metabolon of Saccharomyces cerevisiae allows co-ordinated feedback regulation of the first two steps in arginine biosynthesis.
  Eur J Biochem, 270, 1014-1024.  
12566437 T.Fujita, A.Maggio, M.Garcia-Rios, C.Stauffacher, R.A.Bressan, and L.N.Csonka (2003).
Identification of regions of the tomato gamma-glutamyl kinase that are involved in allosteric regulation by proline.
  J Biol Chem, 278, 14203-14210.  
12351849 F.Gil-Ortiz, I.Fita, S.Ramón-Maiques, A.Marina, and V.Rubio (2002).
A crystallographic glimpse of a nucleotide triphosphate (AMPPNP) bound to a protein surface: external and internal AMPPNP molecules in crystalline N-acetyl-L-glutamate kinase.
  Acta Crystallogr D Biol Crystallogr, 58, 1892-1895.  
12037312 M.L.Fernández-Murga, S.Ramón-Maiques, F.Gil-Ortiz, I.Fita, and V.Rubio (2002).
Towards structural understanding of feedback control of arginine biosynthesis: cloning and expression of the gene for the arginine-inhibited N-acetyl-L-glutamate kinase from Pseudomonas aeruginosa, purification and crystallization of the recombinant enzyme and preliminary X-ray studies.
  Acta Crystallogr D Biol Crystallogr, 58, 1045-1047.  
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 codes are shown on the right.