Database accession: MF7000650
Name: LcCOMT with SAH
PDB ID: 7v6l
Experimental method: X-ray (1.95 Å)
Assembly: Homodimer
Source organism: Ligusticum sinense
Primary publication of the structure:
Song S, Chen A, Zhu J, Yan Z, An Q, Zhou J, Liao H, Yu Y
Structure basis of the caffeic acid O-methyltransferase from Ligusiticum chuanxiong to understand its selective mechanism.
(2022) Int. J. Biol. Macromol. 194: 317-330
PMID: 34838855
Abstract:
Caffeic acid O-methyltransferase from Ligusticum chuanxiong (LcCOMT) showed strict regiospecificity despite a relative degree of preference. Compared with caffeic acid, methyl caffeate was the preferential substrate by its low Km and high Kcat. In this study, we obtained the SAM binary (1.80 Å) and SAH binary (1.95 Å) complex LcCOMT crystal structures, and established the ternary complex structure with methyl caffeate by molecular docking. The active site of LcCOMT included phenolic substrate pocket, SAM/SAH ligand pocket and conserved catalytic residues as well. The regiospecificity of LcCOMT that permitted only 3-hydroxyl group to be methylated arise from the interactions between the active site and the phenyl ring. However, the propanoid tail governed the relative preference of LcCOMT. The ester group in methyl caffeate stabilized the anionic intermediate caused by His268-Asp269 pair, whereas caffeic acid was unable to stabilize the anionic intermediate due to the adjacent carboxylate anion in the propanoid tail. Ser183 residue formed an additional hydrogen bond with SAH and its role was identified by S183A mutation. Ile318 residue might be a potential site for determination of substrate preference, and its mutation led to the change of tertiary conformation. The results supported the selective mechanism of LcCOMT.
Annotations from the GeneOntology database. Only terms that fit at least two of the interacting proteins are shown. Molecular function:
O-methyltransferase activity O-methyltransferase activity
protein dimerization activity protein dimerization activity
S-adenosylmethionine-dependent methyltransferase activity S-adenosylmethionine-dependent methyltransferase activity
Biological process:
aromatic compound biosynthetic process obsolete aromatic compound biosynthetic process
methylation methylation
Cellular component: not assigned
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: Caffeic acid 3-O-methyltransferase
Source organism: Ligusticum sinense
Length: 362 residues
Sequence:Sequence according to the corresponding UniProt protein segmentMNTELIPPTFLEDEEEEACMFAMQLSSASVLPMVLKSAIELNLLESIAKAGPGVYVSPSHLAAGLPSSQPDTPVMLDRILRLLASYSVLNCQLRDLPQGRVERLYGLAPVCKFLTKNSDGVSMAPLLLMNQDKILMESWYHLKDAVLDGGIPFNKAYGMTAFEYHGKDPRFNKVFNQGMSNHSTITMKKILQTYDGFGGLKTVVDVGGGTGATLNMIISKYPNLKGINFDLPHVVEDAPSYPGVEHVGGDMFVSVPKGDAIFMKWICHDWSDAHCLTFLKNCYKALPKDGKVILAECILPEAPDSKLTTKNVIHIDVIMLAHNPGGKERTEKDFEALGKEAGFKSFNKACCAYNTWVIEYYK
UniProtKB AC: A0A0K1YW34 (positions: 13-362)
Coverage: 96%
Name: Caffeic acid 3-O-methyltransferase
Source organism: Ligusticum sinense
Length: 362 residues
Sequence:Sequence according to the corresponding UniProt protein segmentMNTELIPPTFLEDEEEEACMFAMQLSSASVLPMVLKSAIELNLLESIAKAGPGVYVSPSHLAAGLPSSQPDTPVMLDRILRLLASYSVLNCQLRDLPQGRVERLYGLAPVCKFLTKNSDGVSMAPLLLMNQDKILMESWYHLKDAVLDGGIPFNKAYGMTAFEYHGKDPRFNKVFNQGMSNHSTITMKKILQTYDGFGGLKTVVDVGGGTGATLNMIISKYPNLKGINFDLPHVVEDAPSYPGVEHVGGDMFVSVPKGDAIFMKWICHDWSDAHCLTFLKNCYKALPKDGKVILAECILPEAPDSKLTTKNVIHIDVIMLAHNPGGKERTEKDFEALGKEAGFKSFNKACCAYNTWVIEYYK
UniProtKB AC: A0A0K1YW34 (positions: 11-362)
Coverage: 97%
Evidence demonstrating that the participating proteins are unstructured prior to the interaction and their folding is coupled to binding. Representative domain in related structures: Dimeric O-methyltransferase
Evidence level: Indirect evidence
Evidence coverage: Only some parts of the structure participates in mutual synergistic folding.
Complex Evidence:
Coniferyl alcohol 9-O-methyltransferase has an intertwined dimeric structure with large relative interaction surface. The active site is formed by both monomers and thus dimerization is critical for activity. The N-terminal helices form the dimerization subdomain and at the same time form the rear wall of the active-site cavity in the neighbouring monomer (PMID:23633600). Other 9-O-methyltransferase structures show similar features and exhibit no monomeric form in solution (PMID:11224575).
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)
