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PDBsum entry 1ohv

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protein ligands Protein-protein interface(s) links
Transferase PDB id
1ohv
Jmol
Contents
Protein chains
461 a.a. *
Ligands
ACT ×4
PLP ×4
FES ×2
Waters ×633
* Residue conservation analysis
PDB id:
1ohv
Name: Transferase
Title: 4-aminobutyrate-aminotransferase from pig
Structure: 4-aminobutyrate aminotransferase. Chain: a, b, c, d. Fragment: residues 29-500. Synonym: gamma-amino-n-butyrate transaminase, gaba transami gaba aminotransferase, gaba-at, gaba-t. Ec: 2.6.1.19
Source: Sus scrofa. Pig. Organism_taxid: 9823. Organ: liver
Biol. unit: Dimer (from PDB file)
Resolution:
2.30Å     R-factor:   0.188     R-free:   0.221
Authors: P.Storici,T.Schirmer
Key ref:
P.Storici et al. (2004). Structures of gamma-aminobutyric acid (GABA) aminotransferase, a pyridoxal 5'-phosphate, and [2Fe-2S] cluster-containing enzyme, complexed with gamma-ethynyl-GABA and with the antiepilepsy drug vigabatrin. J Biol Chem, 279, 363-373. PubMed id: 14534310 DOI: 10.1074/jbc.M305884200
Date:
02-Jun-03     Release date:   16-Oct-03    
Supersedes: 1gtx
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P80147  (GABT_PIG) -  4-aminobutyrate aminotransferase, mitochondrial
Seq:
Struc:
500 a.a.
461 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class 1: E.C.2.6.1.19  - 4-aminobutyrate--2-oxoglutarate transaminase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: 4-aminobutanoate + 2-oxoglutarate = succinate semialdehyde + L-glutamate
4-aminobutanoate
Bound ligand (Het Group name = ACT)
matches with 57.14% similarity
+ 2-oxoglutarate
= succinate semialdehyde
+ L-glutamate
      Cofactor: Pyridoxal 5'-phosphate
Pyridoxal 5'-phosphate
   Enzyme class 2: E.C.2.6.1.22  - (S)-3-amino-2-methylpropionate transaminase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]

      Pathway:
      Reaction: (S)-3-amino-2-methylpropanoate + 2-oxoglutarate = 2-methyl-3- oxopropanoate + L-glutamate
(S)-3-amino-2-methylpropanoate
Bound ligand (Het Group name = ACT)
matches with 57.14% similarity
+ 2-oxoglutarate
= 2-methyl-3- oxopropanoate
+ L-glutamate
Note, where more than one E.C. class is given (as above), each may correspond to a different protein domain or, in the case of polyprotein precursors, to a different mature protein.
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     4-aminobutyrate transaminase complex   5 terms 
  Biological process     behavioral response to cocaine   4 terms 
  Biochemical function     catalytic activity     8 terms  

 

 
    reference    
 
 
DOI no: 10.1074/jbc.M305884200 J Biol Chem 279:363-373 (2004)
PubMed id: 14534310  
 
 
Structures of gamma-aminobutyric acid (GABA) aminotransferase, a pyridoxal 5'-phosphate, and [2Fe-2S] cluster-containing enzyme, complexed with gamma-ethynyl-GABA and with the antiepilepsy drug vigabatrin.
P.Storici, D.De Biase, F.Bossa, S.Bruno, A.Mozzarelli, C.Peneff, R.B.Silverman, T.Schirmer.
 
  ABSTRACT  
 
Gamma-aminobutyric acid aminotransferase (GABA-AT) is a pyridoxal 5'-phosphate-dependent enzyme responsible for the degradation of the inhibitory neurotransmitter GABA. GABA-AT is a validated target for antiepilepsy drugs because its selective inhibition raises GABA concentrations in brain. The antiepilepsy drug, gamma-vinyl-GABA (vigabatrin) has been investigated in the past by various biochemical methods and resulted in several proposals for its mechanisms of inactivation. In this study we solved and compared the crystal structures of pig liver GABA-AT in its native form (to 2.3-A resolution) and in complex with vigabatrin as well as with the close analogue gamma-ethynyl-GABA (to 2.3 and 2.8 A, respectively). Both inactivators form a covalent ternary adduct with the active site Lys-329 and the pyridoxal 5'-phosphate (PLP) cofactor. The crystal structures provide direct support for specific inactivation mechanisms proposed earlier on the basis of radio-labeling experiments. The reactivity of GABA-AT crystals with the two GABA analogues was also investigated by polarized absorption microspectrophotometry. The spectral data are discussed in relation to the proposed mechanism. Intriguingly, all cluster of yet unknown function at the center of the dimeric molecule in the vicinity of the PLP cofactors.
 
  Selected figure(s)  
 
Figure 1.
FIG. 1. Stereographic projection of the active site of GABA-AT. The final model is shown together with the 2F[o] - F[c] map (contour level, 1.2 ). An acetate molecule is found close to Arg-192, i.e. at a position where the carboxylate moiety of the natural substrate GABA is expected to bind (6).
Figure 3.
FIG. 3. The [2Fe-2S] cluster at the center of the GABA-AT dimer. A, structure of the GABA-AT dimer. The view is approximately along the molecular 2-fold symmetry axis. The C traces of the two subunits are shown in black and red. Helix 5 and its symmetry mate are highlighted by thick gray traces. The [2Fe-2S] cluster on the molecular 2-fold symmetry axis together with the liganding cysteines and the two symmetry related PLP cofactors are shown in full view. B, close-up view of A. The C traces have been omitted for clarity. Symmetry-related residues are marked with the symbol "#." C, stereographic close-up view. The molecular 2-fold axis is approximately along the vertical direction. The native 2F[o] - F[c] omit map (magenta; contour level 1.2 ) and the anomalous difference map (light blue; contour level 4.5 ) were computed with data to 2.3-Å resolution (data set of the vigabatrin complex). The iron and sulfur atoms were not included for phasing.
 
  The above figures are reprinted by permission from the ASBMB: J Biol Chem (2004, 279, 363-373) copyright 2004.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
22505258 J.J.Headd, N.Echols, P.V.Afonine, R.W.Grosse-Kunstleve, V.B.Chen, N.W.Moriarty, D.C.Richardson, J.S.Richardson, and P.D.Adams (2012).
Use of knowledge-based restraints in phenix.refine to improve macromolecular refinement at low resolution.
  Acta Crystallogr D Biol Crystallogr, 68, 381-390.  
20673774 R.E.Hubbard (2011).
Structure-based drug discovery and protein targets in the CNS.
  Neuropharmacology, 60, 7.  
19197387 I.B.Müller, F.Wu, B.Bergmann, J.Knöckel, R.D.Walter, H.Gehring, and C.Wrenger (2009).
Poisoning pyridoxal 5-phosphate-dependent enzymes: a new strategy to target the malaria parasite Plasmodium falciparum.
  PLoS ONE, 4, e4406.  
19300440 Y.G.Kim, S.Lee, O.S.Kwon, S.Y.Park, S.J.Lee, B.J.Park, and K.J.Kim (2009).
Redox-switch modulation of human SSADH by dynamic catalytic loop.
  EMBO J, 28, 959-968.
PDB codes: 2w8n 2w8o 2w8p 2w8q 2w8r
  19727327 D.B.Berkowitz, K.R.Karukurichi, R.de la Salud-Bea, D.L.Nelson, and C.D.McCune (2008).
Use of Fluorinated Functionality in Enzyme Inhibitor Development: Mechanistic and Analytical Advantages.
  J Fluor Chem, 129, 731-742.  
17988865 M.D.Clift, and R.B.Silverman (2008).
Synthesis and evaluation of novel aromatic substrates and competitive inhibitors of GABA aminotransferase.
  Bioorg Med Chem Lett, 18, 3122-3125.  
19359804 R.Meguro, Y.Asano, S.Odagiri, C.Li, and K.Shoumura (2008).
Cellular and subcellular localizations of nonheme ferric and ferrous iron in the rat brain: a light and electron microscopic study by the perfusion-Perls and -Turnbull methods.
  Arch Histol Cytol, 71, 205-222.  
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
17212389 K.R.Karukurichi, R.de la Salud-Bea, W.J.Jahng, and D.B.Berkowitz (2007).
Examination of the new alpha-(2'Z-fluoro)vinyl trigger with lysine decarboxylase: the absolute stereochemistry dictates the reaction course.
  J Am Chem Soc, 129, 258-259.  
17988152 M.D.Clift, H.Ji, G.P.Deniau, D.O'Hagan, and R.B.Silverman (2007).
Enantiomers of 4-amino-3-fluorobutanoic acid as substrates for gamma-aminobutyric acid aminotransferase. Conformational probes for GABA binding.
  Biochemistry, 46, 13819-13828.  
17323931 Q.Wu, Y.N.Liu, H.Chen, E.J.Molitor, and H.W.Liu (2007).
A retro-evolution study of CDP-6-deoxy-D-glycero-L-threo-4-hexulose-3-dehydrase (E1) from Yersinia pseudotuberculosis: implications for C-3 deoxygenation in the biosynthesis of 3,6-dideoxyhexoses.
  Biochemistry, 46, 3759-3767.  
16494487 D.B.Berkowitz, B.Wu, and H.Li (2006).
A formal [3,3]-sigmatropic rearrangement route to quaternary alpha-vinyl amino acids: use of allylic N-PMP trifluoroacetimidates.
  Org Lett, 8, 971-974.  
  16754985 S.M.Tripathi, and R.Ramachandran (2006).
Overexpression, purification and crystallization of lysine epsilon-aminotransferase (Rv3290c) from Mycobacterium tuberculosis H37Rv.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 62, 572-575.  
  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.  
15672674 R.O.Beleboni, R.O.Carolino, A.B.Pizzo, L.Castellan-Baldan, J.Coutinho-Netto, W.F.dos Santos, and N.C.Coimbra (2004).
Pharmacological and biochemical aspects of GABAergic neurotransmission: pathological and neuropsychobiological relationships.
  Cell Mol Neurobiol, 24, 707-728.  
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.