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PDBsum entry 2gsa

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protein ligands Protein-protein interface(s) links
Chlorophyll biosynthesis PDB id
2gsa
Jmol
Contents
Protein chains
427 a.a. *
Ligands
PMP
PLP
Waters ×347
* Residue conservation analysis
PDB id:
2gsa
Name: Chlorophyll biosynthesis
Title: Crystal structure of glutamate-1-semialdehyde aminomutase (aminotransferase, wild-type form)
Structure: Glutamate semialdehyde aminotransferase. Chain: a, b. Synonym: glutamate semialdehyde aminomutase. Engineered: yes
Source: Synechococcus sp.. Organism_taxid: 1131. Strain: gr6. Expressed in: escherichia coli. Expression_system_taxid: 562.
Biol. unit: Homo-Dimer (from PDB file)
Resolution:
2.40Å     R-factor:   0.183     R-free:   0.250
Authors: M.Hennig,J.N.Jansonius
Key ref:
M.Hennig et al. (1997). Crystal structure of glutamate-1-semialdehyde aminomutase: an alpha2-dimeric vitamin B6-dependent enzyme with asymmetry in structure and active site reactivity. Proc Natl Acad Sci U S A, 94, 4866-4871. PubMed id: 9144156 DOI: 10.1073/pnas.94.10.4866
Date:
26-Feb-97     Release date:   04-Mar-98    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P24630  (GSA_SYNP6) -  Glutamate-1-semialdehyde 2,1-aminomutase
Seq:
Struc:
433 a.a.
427 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 5 residue positions (black crosses)

 Enzyme reactions 
   Enzyme class: E.C.5.4.3.8  - Glutamate-1-semialdehyde 2,1-aminomutase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]

      Pathway:
Porphyrin Biosynthesis (early stages)
      Reaction: (S)-4-amino-5-oxopentanoate = 5-aminolevulinate
(S)-4-amino-5-oxopentanoate
=
5-aminolevulinate
Bound ligand (Het Group name = PMP)
matches with 47.06% similarity
      Cofactor: Pyridoxal 5'-phosphate
Pyridoxal 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     tetrapyrrole biosynthetic process   4 terms 
  Biochemical function     catalytic activity     5 terms  

 

 
    reference    
 
 
DOI no: 10.1073/pnas.94.10.4866 Proc Natl Acad Sci U S A 94:4866-4871 (1997)
PubMed id: 9144156  
 
 
Crystal structure of glutamate-1-semialdehyde aminomutase: an alpha2-dimeric vitamin B6-dependent enzyme with asymmetry in structure and active site reactivity.
M.Hennig, B.Grimm, R.Contestabile, R.A.John, J.N.Jansonius.
 
  ABSTRACT  
 
The three-dimensional structure of glutamate-1-semialdehyde aminomutase (EC 5.4.3.8), an alpha2-dimeric enzyme from Synechococcus, has been determined by x-ray crystallography using heavy atom derivative phasing. The structure, refined at 2.4-A resolution to an R-factor of 18.7% and good stereochemistry, explains many of the enzyme's unusual specificity and functional properties. The overall fold is that of aspartate aminotransferase and related B6 enzymes, but it also has specific features. The structure of the complex with gabaculine, a substrate analogue, shows unexpectedly that the substrate binding site involves residues from the N-terminal domain of the molecule, notably Arg-32. Glu-406 is suitably positioned to repel alpha-carboxylic acids, thereby suggesting a basis for the enzyme's reaction specificity. The subunits show asymmetry in cofactor binding and in the mobilities of the residues 153-181. In the unliganded enzyme, one subunit has the cofactor bound as an aldimine of pyridoxal phosphate with Lys-273 and, in this subunit, residues 153-181 are disordered. In the other subunit in which the cofactor is not covalently bound, residues 153-181 are well defined. Consistent with the crystallographically demonstrated asymmetry, a form of the enzyme in which both subunits have pyridoxal phosphate bound to Lys-273 through a Schiff base showed biphasic reduction by borohydride in solution. Analysis of absorption spectra during reduction provided evidence of communication between the subunits. The crystal structure of the reduced form of the enzyme shows that, despite identical cofactor binding in each monomer, the structural asymmetry at residues 153-181 remains.
 
  Selected figure(s)  
 
Figure 1.
Fig. 1. Intermediates in the conversion of GSA to 5-aminolevulinate. R, (CH[2])[2]COO ; Py, the 5 -phosphopyridoxyl group of the cofactor.
Figure 6.
Fig. 6. Active site of subunit A with gabaculine noncovalently bound, superimposed on a 3.0-Å resolution omit map, contoured at 4^ .
 
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20506125 G.Layer, J.Reichelt, D.Jahn, and D.W.Heinz (2010).
Structure and function of enzymes in heme biosynthesis.
  Protein Sci, 19, 1137-1161.  
17680699 V.Rajaram, P.Ratna Prasuna, H.S.Savithri, and M.R.Murthy (2008).
Structure of biosynthetic N-acetylornithine aminotransferase from Salmonella typhimurium: studies on substrate specificity and inhibitor binding.
  Proteins, 70, 429-441.
PDB codes: 2pb0 2pb2
17259358 J.Kim, D.Kyung, H.Yun, B.K.Cho, J.H.Seo, M.Cha, and B.G.Kim (2007).
Cloning and characterization of a novel beta-transaminase from Mesorhizobium sp. strain LUK: a new biocatalyst for the synthesis of enantiomerically pure beta-amino acids.
  Appl Environ Microbiol, 73, 1772-1782.  
17185223 B.Julien, Z.Q.Tian, R.Reid, and C.D.Reeves (2006).
Analysis of the ambruticin and jerangolid gene clusters of Sorangium cellulosum reveals unusual mechanisms of polyketide biosynthesis.
  Chem Biol, 13, 1277-1286.  
16954186 J.Stetefeld, M.Jenny, and P.Burkhard (2006).
Intersubunit signaling in glutamate-1-semialdehyde-aminomutase.
  Proc Natl Acad Sci U S A, 103, 13688-13693.
PDB codes: 2hoy 2hoz 2hp1 2hp2
  17012789 V.Rajaram, K.Prasad, P.Ratna Prasuna, N.Ramachandra, S.R.Bharath, H.S.Savithri, and M.R.Murthy (2006).
Cloning, purification, crystallization and preliminary X-ray crystallographic analysis of the biosynthetic N-acetylornithine aminotransferases from Salmonella typhimurium and Escherichia coli.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 62, 980-983.  
  16682782 X.Lv, J.Fan, H.Ge, Y.Gao, X.Zhang, M.Teng, and L.Niu (2006).
Cloning, expression, purification, crystallization and preliminary X-ray diffraction analysis of the glutamate-1-semialdehyde aminotransferase from Bacillus subtilis.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 62, 483-485.  
16339726 A.Atteia, R.van Lis, and S.I.Beale (2005).
Enzymes of the heme biosynthetic pathway in the nonphotosynthetic alga Polytomella sp.
  Eukaryot Cell, 4, 2087-2097.  
16121195 I.Astner, J.O.Schulze, J.van den Heuvel, D.Jahn, W.D.Schubert, and D.W.Heinz (2005).
Crystal structure of 5-aminolevulinate synthase, the first enzyme of heme biosynthesis, and its link to XLSA in humans.
  EMBO J, 24, 3166-3177.
PDB codes: 2bwn 2bwo 2bwp
15189147 A.C.Eliot, and J.F.Kirsch (2004).
Pyridoxal phosphate enzymes: mechanistic, structural, and evolutionary considerations.
  Annu Rev Biochem, 73, 383-415.  
15498941 A.Paiardini, F.Bossa, and S.Pascarella (2004).
Evolutionarily conserved regions and hydrophobic contacts at the superfamily level: The case of the fold-type I, pyridoxal-5'-phosphate-dependent enzymes.
  Protein Sci, 13, 2992-3005.  
12777822 P.Kongsaeree, C.Samanchart, P.Laowanapiban, S.Wiyakrutta, and V.Meevootisom (2003).
Crystallization and preliminary X-ray crystallographic analysis of d-phenylglycine aminotransferase from Pseudomonas stutzeri ST201.
  Acta Crystallogr D Biol Crystallogr, 59, 953-954.  
12010463 D.V.Vavilin, and W.F.Vermaas (2002).
Regulation of the tetrapyrrole biosynthetic pathway leading to heme and chlorophyll in plants and cyanobacteria.
  Physiol Plant, 115, 9.  
11327867 A.J.Lloyd, and P.M.Shoolingin-Jordan (2001).
Dimeric pig heart succinate-coenzyme A transferase uses only one subunit to support catalysis.
  Biochemistry, 40, 2455-2467.  
11726494 J.Moser, W.D.Schubert, V.Beier, I.Bringemeier, D.Jahn, and D.W.Heinz (2001).
V-shaped structure of glutamyl-tRNA reductase, the first enzyme of tRNA-dependent tetrapyrrole biosynthesis.
  EMBO J, 20, 6583-6590.
PDB code: 1gpj
11933244 K.Soda, T.Yoshimura, and N.Esaki (2001).
Stereospecificity for the hydrogen transfer of pyridoxal enzyme reactions.
  Chem Rec, 1, 373-384.  
11685243 P.Burkhard, P.Dominici, C.Borri-Voltattorni, J.N.Jansonius, and V.N.Malashkevich (2001).
Structural insight into Parkinson's disease treatment from drug-inhibited DOPA decarboxylase.
  Nat Struct Biol, 8, 963-967.
PDB codes: 1js3 1js6
11737206 R.Contestabile, A.Paiardini, S.Pascarella, M.L.di Salvo, S.D'Aguanno, and F.Bossa (2001).
l-Threonine aldolase, serine hydroxymethyltransferase and fungal alanine racemase. A subgroup of strictly related enzymes specialized for different functions.
  Eur J Biochem, 268, 6508-6525.  
10673430 G.Schneider, H.Käck, and Y.Lindqvist (2000).
The manifold of vitamin B6 dependent enzymes.
  Structure, 8, R1-R6.  
10715130 R.Contestabile, T.Jenn, M.Akhtar, D.Gani, and R.A.John (2000).
Reactions of glutamate 1-semialdehyde aminomutase with R- and S-enantiomers of a novel, mechanism-based inhibitor, 2,3-diaminopropyl sulfate.
  Biochemistry, 39, 3091-3096.  
10684605 T.Fujii, M.Maeda, H.Mihara, T.Kurihara, N.Esaki, and Y.Hata (2000).
Structure of a NifS homologue: X-ray structure analysis of CsdB, an Escherichia coli counterpart of mammalian selenocysteine lyase.
  Biochemistry, 39, 1263-1273.
PDB code: 1c0n
10378276 A.D.Kern, M.A.Oliveira, P.Coffino, and M.L.Hackert (1999).
Structure of mammalian ornithine decarboxylase at 1.6 A resolution: stereochemical implications of PLP-dependent amino acid decarboxylases.
  Structure, 7, 567-581.
PDB code: 7odc
10584065 A.Poupon, F.Jebai, G.Labesse, F.Gros, J.Thibault, J.P.Mornon, and M.Krieger (1999).
Structure modelling and site-directed mutagenesis of the rat aromatic L-amino acid pyridoxal 5'-phosphate-dependent decarboxylase: a functional study.
  Proteins, 37, 191-203.  
10387080 J.N.Scarsdale, G.Kazanina, S.Radaev, V.Schirch, and H.T.Wright (1999).
Crystal structure of rabbit cytosolic serine hydroxymethyltransferase at 2.8 A resolution: mechanistic implications.
  Biochemistry, 38, 8347-8358.
PDB code: 1cj0
10393538 P.Storici, G.Capitani, D.De Biase, M.Moser, R.A.John, J.N.Jansonius, and T.Schirmer (1999).
Crystal structure of GABA-aminotransferase, a target for antiepileptic drug therapy.
  Biochemistry, 38, 8628-8634.
PDB code: 1gtx
9914259 J.N.Jansonius (1998).
Structure, evolution and action of vitamin B6-dependent enzymes.
  Curr Opin Struct Biol, 8, 759-769.  
9772188 K.H.Jhee, P.McPhie, H.S.Ro, and E.W.Miles (1998).
Tryptophan synthase mutations that alter cofactor chemistry lead to mechanism-based inactivation.
  Biochemistry, 37, 14591-14604.  
  9605314 K.Qu, D.L.Martin, and C.E.Lawrence (1998).
Motifs and structural fold of the cofactor binding site of human glutamate decarboxylase.
  Protein Sci, 7, 1092-1105.  
9628737 S.L.Clugston, J.F.Barnard, R.Kinach, D.Miedema, R.Ruman, E.Daub, and J.F.Honek (1998).
Overproduction and characterization of a dimeric non-zinc glyoxalase I from Escherichia coli: evidence for optimal activation by nickel ions.
  Biochemistry, 37, 8754-8763.  
  9761478 S.Pascarella, S.Angelaccio, R.Contestabile, S.Delle Fratte, M.Di Salvo, and F.Bossa (1998).
The structure of serine hydroxymethyltransferase as modeled by homology and validated by site-directed mutagenesis.
  Protein Sci, 7, 1976-1982.  
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.