Database accession: MF7000132
Name: CaiB (Type III CoA transferase in carnitine metabolism)
PDB ID: 1xa4
Experimental method: X-ray (1.90 Å)
Assembly: Homodimer
Source organism: Escherichia coli
Primary publication of the structure:
Stenmark P, Gurmu D, Nordlund P
Crystal structure of CaiB, a type-III CoA transferase in carnitine metabolism.
(2004) Biochemistry 43: 13996-4003
PMID: 15518548
Abstract:
Carnitine is an important molecule in human metabolism, mainly because of its role in the transport of long-chain fatty acids across the inner mitochondrial membrane. Escherichia coli uses carnitine as a terminal electron acceptor during anaerobic metabolism. Bacteria present in our large intestine break down carnitine that is not absorbed in the small intestine. One part of this catabolic pathway is reversible and can be utilized for bioproduction of large amounts of stereochemically pure L-carnitine, which is used medically for the treatment of a variety of human diseases. Here, we present the crystal structure of the E. coli protein CaiB, which is a member of the recently identified type-III coenzyme A (CoA) transferase family and catalyzes the transfer of the CoA moiety between gamma-butyrobetaine-CoA and carnitine forming carnityl-CoA and gamma-butyrobetaine. This is the first protein from the carnitine metabolic pathway to be structurally characterized. The structure of CaiB reveals a spectacular fold where two monomers are interlaced to form an interlocked dimer. A molecule of the crystallization buffer bis-(2-hydroxyethyl)imino-tris(hydroxymethyl)methane (bis-tris) is bound in a large pocket located primarily in the small domain, and we propose that this pocket constitutes the binding site for both substrate moieties participating in the CaiB transfer reaction. The binding of CoA to CaiB induces a domain movement that closes the active site of the protein. This is the first observation of a domain movement in the type-III CoA transferase family and can play an important role in coupling substrate binding to initiation of the catalytic reaction.
Annotations from the GeneOntology database. Only terms that fit at least two of the interacting proteins are shown. Molecular function:
L-carnitine CoA-transferase activity L-carnitine CoA-transferase activity
Biological process:
carnitine catabolic process carnitine catabolic process
Cellular component:
cytoplasm cytoplasm
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: L-carnitine CoA-transferase
Source organism: Escherichia coli
Length: 405 residues
Sequence:Sequence according to the corresponding UniProt protein segmentMDHLPMPKFGPLAGLRVVFSGIEIAGPFAGQMFAEWGAEVIWIENVAWADTIRVQPNYPQLSRRNLHALSLNIFKDEGREAFLKLMETTDIFIEASKGPAFARRGITDEVLWQHNPKLVIAHLSGFGQYGTEEYTNLPAYNTIAQAFSGYLIQNGDVDQPMPAFPYTADYFSGLTATTAALAALHKVRETGKGESIDIAMYEVMLRMGQYFMMDYFNGGEMCPRMSKGKDPYYAGCGLYKCADGYIVMELVGITQIEECFKDIGLAHLLGTPEIPEGTQLIHRIECPYGPLVEEKLDAWLATHTIAEVKERFAELNIACAKVLTVPELESNPQYVARESITQWQTMDGRTCKGPNIMPKFKNNPGQIWRGMPSHGMDTAAILKNIGYSENDIQELVSKGLAKVED
UniProtKB AC: P31572 (positions: 4-403)
Coverage: 98%
Name: L-carnitine CoA-transferase
Source organism: Escherichia coli
Length: 405 residues
Sequence:Sequence according to the corresponding UniProt protein segmentMDHLPMPKFGPLAGLRVVFSGIEIAGPFAGQMFAEWGAEVIWIENVAWADTIRVQPNYPQLSRRNLHALSLNIFKDEGREAFLKLMETTDIFIEASKGPAFARRGITDEVLWQHNPKLVIAHLSGFGQYGTEEYTNLPAYNTIAQAFSGYLIQNGDVDQPMPAFPYTADYFSGLTATTAALAALHKVRETGKGESIDIAMYEVMLRMGQYFMMDYFNGGEMCPRMSKGKDPYYAGCGLYKCADGYIVMELVGITQIEECFKDIGLAHLLGTPEIPEGTQLIHRIECPYGPLVEEKLDAWLATHTIAEVKERFAELNIACAKVLTVPELESNPQYVARESITQWQTMDGRTCKGPNIMPKFKNNPGQIWRGMPSHGMDTAAILKNIGYSENDIQELVSKGLAKVED
UniProtKB AC: P31572 (positions: 4-403)
Coverage: 98%
Evidence demonstrating that the participating proteins are unstructured prior to the interaction and their folding is coupled to binding. Representative domain in related structures: CoA-transferase family III
Evidence level: Indirect evidence
Evidence coverage: The full structure participates in mutual synergistic folding.
Complex Evidence:
The structure of CaiB reveals a spectacular fold where two monomers are interlaced to form an interlocked dimer with large interface (PMID:15518548). The folding path of CaiB and other proteins of this fold must be quite complex because the dimer cannot be formed by the individually folded monomers, partial unfolding would have to take place to break the CaiB dimer, thus it is most probably very stable (PMID:15518548).
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)
