4UY7

Crystal structure of Histidine bound Histidine-specific methyltransferase EgtD from Mycobacterium smegmatis

Summary for 4UY7

• Entry DOI: 10.2210/pdb4uy7/pdb
• Related: 4UY5 4UY6 4UZ0
• Descriptor: HISTIDINE-SPECIFIC METHYLTRANSFERASE EGTD, HISTIDINE (3 entities in total)
• Functional Keywords: transferase, antioxidant
• Biological source: MYCOBACTERIUM SMEGMATIS
• Total number of polymer chains: 2
• Total formula weight: 72273.18

Authors

Jeong, J.H.,Kim, Y.G. (deposition date: 2014-08-29, release date: 2014-10-08, Last modification date: 2024-01-10)

Primary citation

Jeong, J.H.,Cha, H.J.,Ha, S.C.,Rojviriya, C.,Kim, Y.G.
Structural Insights Into the Histidine Trimethylation Activity of Egtd from Mycobacterium Smegmatis.
Biochem.Biophys.Res.Commun., 452:1098-, 2014

PubMed Abstract: EgtD is an S-adenosyl-l-methionine (SAM)-dependent histidine N,N,N-methyltransferase that catalyzes the formation of hercynine from histidine in the ergothioneine biosynthetic process of Mycobacterium smegmatis. Ergothioneine is a secreted antioxidant that protects mycobacterium from oxidative stress. Here, we present three crystal structures of EgtD in the apo form, the histidine-bound form, and the S-adenosyl-l-homocysteine (SAH)/histidine-bound form. The study revealed that EgtD consists of two distinct domains: a typical methyltransferase domain and a unique substrate binding domain. The histidine binding pocket of the substrate binding domain primarily recognizes the imidazole ring and carboxylate group of histidine rather than the amino group, explaining the high selectivity for histidine and/or (mono-, di-) methylated histidine as substrates. In addition, SAM binding to the MTase domain induced a conformational change in EgtD to facilitate the methyl transfer reaction. The structural analysis provides insights into the putative catalytic mechanism of EgtD in a processive trimethylation reaction.

PubMed: 25251321
DOI: 10.1016/J.BBRC.2014.09.058

Experimental method

X-RAY DIFFRACTION (2.306 Å)