Database accession: MF2110019
Name: 4-aminobutyrate aminotransferase
PDB ID: 1ohv
Experimental method: X-ray (2.30 Å)
Assembly: Homodimer
Source organism: Sus scrofa
Primary publication of the structure:
Storici P, De Biase D, Bossa F, Bruno S, Mozzarelli A, Peneff C, Silverman RB, Schirmer T
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.
(2004) J. Biol. Chem. 279: 363-73
PMID: 14534310
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 three structures revealed a [2Fe-2S] cluster of yet unknown function at the center of the dimeric molecule in the vicinity of the PLP cofactors.
Annotations from the GeneOntology database. Only terms that fit at least two of the interacting proteins are shown. Molecular function:
(S)-3-amino-2-methylpropionate transaminase activity (S)-3-amino-2-methylpropionate transaminase activity
2 iron, 2 sulfur cluster binding 2 iron, 2 sulfur cluster binding
4-aminobutyrate transaminase activity 4-aminobutyrate transaminase activity
4-aminobutyrate 4-aminobutyrate:2-oxoglutarate transaminase activity
identical protein binding identical protein binding
metal ion binding metal ion binding
protein homodimerization activity protein homodimerization activity
pyridoxal phosphate binding pyridoxal phosphate binding
succinate-semialdehyde dehydrogenase binding succinate-semialdehyde dehydrogenase binding
Biological process:
behavioral response to cocaine behavioral response to cocaine
gamma-aminobutyric acid catabolic process gamma-aminobutyric acid catabolic process
Cellular component:
4-aminobutyrate transaminase complex 4-aminobutyrate transaminase complex
cytosol cytosol
mitochondrial matrix mitochondrial matrix
mitochondrion mitochondrion
Structural annotations of the participating protein chains.Entry contents: 2 distinct polypeptide molecules
Chains: A, B
Notes: All chains according to the most probable oligomerization state stored in PDBe were considered.
Number of unique protein segments: 1
Name: 4-aminobutyrate aminotransferase, mitochondrial
Source organism: Sus scrofa
Length: 500 residues
Sequence:Sequence according to the corresponding UniProt protein segmentMASVLLTRRLACSFRHNHRLLVPGWRHISQAAAKVDVEFDYDGPLMKTEVPGPRSRELMKQLNIIQNAEAVHFFCNYEESRGNYLVDVDGNRMLDLYSQISSIPIGYSHPALVKLVQQPQNVSTFINRPALGILPPENFVEKLRESLLSVAPKGMSQLITMACGSCSNENAFKTIFMWYRSKERGQSAFSKEELETCMINQAPGCPDYSILSFMGAFHGRTMGCLATTHSKAIHKIDIPSFDWPIAPFPRLKYPLEEFVKENQQEEARCLEEVEDLIVKYRKKKKTVAGIIVEPIQSEGGDNHASDDFFRKLRDISRKHGCAFLVDEVQTGGGSTGKFWAHEHWGLDDPADVMTFSKKMMTGGFFHKEEFRPNAPYRIFNTWLGDPSKNLLLAEVINIIKREDLLSNAAHAGKVLLTGLLDLQARYPQFISRVRGRGTFCSFDTPDESIRNKLISIARNKGVMLGGCGDKSIRFRPTLVFRDHHAHLFLNIFSDILADFK
UniProtKB AC: P80147 (positions: 39-499)
Coverage: 92%
Name: 4-aminobutyrate aminotransferase, mitochondrial
Source organism: Sus scrofa
Length: 500 residues
Sequence:Sequence according to the corresponding UniProt protein segmentMASVLLTRRLACSFRHNHRLLVPGWRHISQAAAKVDVEFDYDGPLMKTEVPGPRSRELMKQLNIIQNAEAVHFFCNYEESRGNYLVDVDGNRMLDLYSQISSIPIGYSHPALVKLVQQPQNVSTFINRPALGILPPENFVEKLRESLLSVAPKGMSQLITMACGSCSNENAFKTIFMWYRSKERGQSAFSKEELETCMINQAPGCPDYSILSFMGAFHGRTMGCLATTHSKAIHKIDIPSFDWPIAPFPRLKYPLEEFVKENQQEEARCLEEVEDLIVKYRKKKKTVAGIIVEPIQSEGGDNHASDDFFRKLRDISRKHGCAFLVDEVQTGGGSTGKFWAHEHWGLDDPADVMTFSKKMMTGGFFHKEEFRPNAPYRIFNTWLGDPSKNLLLAEVINIIKREDLLSNAAHAGKVLLTGLLDLQARYPQFISRVRGRGTFCSFDTPDESIRNKLISIARNKGVMLGGCGDKSIRFRPTLVFRDHHAHLFLNIFSDILADFK
UniProtKB AC: P80147 (positions: 39-499)
Coverage: 92%
Evidence demonstrating that the participating proteins are unstructured prior to the interaction and their folding is coupled to binding. Representative domain in related structures: Aminotransferase class-III
Evidence level: Direct evidence
Evidence coverage: The full structure participates in mutual synergistic folding.
Complex Evidence:
The equilibrium unfolding of pig liver 4-aminobutyrate aminotransferase by urea was found to be a cooperative process. The kinetic results indicated that the aminotransferase unfolds in a single kinetic phase (PMID:8075151).
Chain A:
N/A
Chain B:
N/A
Surface and contacts features:
Structures from the PDB that contain the same number of proteins, and the proteins from the two structures show a sufficient degree of pairwise similarity, i.e. they belong to the same UniRef90 cluster (the full proteins exhibit at least 90% sequence identity) and convey roughly the same region to their respective interactions (the two regions from the two proteins share a minimum of 70% overlap). Download the CIF file (.cif)
Download this entry's XML file (.xml)
Download this entry's JSON file (.json)
