Database accession: MF7000134
Name: CaiB (Type III CoA transferase in carnitine metabolism), D169A mutant /CoA complex
PDB ID: 1xvu
Experimental method: X-ray (2.40 Å)
Assembly: Homodimer
Source organism: Escherichia coli
Primary publication of the structure:
Rangarajan ES, Li Y, Iannuzzi P, Cygler M, Matte A
Crystal structure of Escherichia coli crotonobetainyl-CoA: carnitine CoA-transferase (CaiB) and its complexes with CoA and carnitinyl-CoA.
(2005) Biochemistry 44: 5728-38
PMID: 15823031
Abstract:
L-Carnitine (R-[-]-3-hydroxy-4-trimethylaminobutyrate) is found in both eukaryotic and prokaryotic cells and participates in diverse processes including long-chain fatty-acid transport and osmoprotection. The enzyme crotonobetainyl/gamma-butyrobetainyl-CoA:carnitine CoA-transferase (CaiB; E.C. 2.8.3.-) catalyzes the first step in carnitine metabolism, leading to the final product gamma-butyrobetaine. The crystal structures of Escherichia coli apo-CaiB, as well as its Asp169Ala mutant bound to CoA and to carnitinyl-CoA, have been determined and refined to 1.6, 2.4, and 2.4 A resolution, respectively. CaiB is composed of two identical circular chains that together form an intertwined dimer. Each monomer consists of a large domain, containing a Rossmann fold, and a small domain. The monomer and dimer resemble those of formyl-CoA transferase from Oxalobacter formigenes, as well as E. coli YfdW, a putative type-III CoA transferase of unknown function. The CoA cofactor-binding site is formed at the interface of the large domain of one monomer and the small domain from the second monomer. Most of the protein-CoA interactions are formed with the Rossmann fold domain. While the location of cofactor binding is similar in the three proteins, the specific CoA-protein interactions vary somewhat between CaiB, formyl-CoA transferase, and YfdW. CoA binding results in a change in the relative positions of the large and small domains compared with apo-CaiB. The observed carnitinyl-CoA product in crystals of the CaiB Asp169Ala mutant cocrystallized with crotonoyl-CoA and carnitine could result from (i) a catalytic mechanism involving a ternary enzyme-substrate complex, independent of a covalent anhydride intermediate with Asp169, (ii) a spontaneous reaction of the substrates in solution, followed by binding to the enzyme, or (iii) an involvement of another residue substituting functionally for Asp169, such as Glu23.
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, A-2
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: 4-405)
Coverage: 99%
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: 4-405)
Coverage: 99%
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 A-2:
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)
