6IWT

Crystal structure of methyltransferase COMT-S in P. praeruptorum

Summary for 6IWT

• Entry DOI: 10.2210/pdb6iwt/pdb
• Descriptor: Pmethyltransferase pCOMT-S, DI(HYDROXYETHYL)ETHER (3 entities in total)
• Functional Keywords: o-methyltransferase, o-methylation, evolution, transferase
• Biological source: Peucedanum praeruptorum
• Total number of polymer chains: 2
• Total formula weight: 80257.17

Authors

Wang, N.N.,Zeng, Z.X. (deposition date: 2018-12-06, release date: 2019-04-03, Last modification date: 2023-11-22)

Primary citation

Zhao, Y.,Wang, N.,Sui, Z.,Huang, C.,Zeng, Z.,Kong, L.
The Molecular and Structural Basis ofO-methylation Reaction in Coumarin Biosynthesis inPeucedanum praeruptorumDunn.
Int J Mol Sci, 20:-, 2019

PubMed Abstract: Methoxylated coumarins represent a large proportion of officinal value coumarins while only one enzyme specific to bergaptol -methylation (BMT) has been identified to date. The multiple types of methoxylated coumarins indicate that at least one unknown enzyme participates in the -methylation of other hydroxylated coumarins and remains to be identified. Combined transcriptome and metabonomics analysis revealed that an enzyme similar to caffeic acid -methyltransferase (COMT-S, S is short for similar) was involved in catalyzing all the hydroxylated coumarins in . However, the precise molecular mechanism of its substrate heterozygosis remains unsolved. Pursuing this question, we determined the crystal structure of COMT-S to clarify its substrate preference. The result revealed that Asn132, Asp271, and Asn325 govern the substrate heterozygosis of COMT-S. A single mutation, such as N132A, determines the catalytic selectivity of hydroxyl groups in esculetin and also causes production differences in bergapten. Evolution-based analysis indicated that BMT was only recently derived as a paralogue of caffeic acid -methyltransferase (COMT) via gene duplication, occurring before the Apiaceae family divergence between 37 and 100 mya. The present study identified the previously unknown -methylation steps in coumarin biosynthesis. The crystallographic and mutational studies provided a deeper understanding of the substrate preference, which can be used for producing specific -methylation coumarins. Moreover, the evolutionary relationship between BMT and COMT-S was clarified to facilitate understanding of evolutionary events in the Apiaceae family.

PubMed: 30934718
DOI: 10.3390/ijms20071533

Experimental method

X-RAY DIFFRACTION (2.53 Å)