5T67

x-ray structure of the KijD1 C3-methyltransferase from Actinomadura kijaniata in complex with SAH and dTDP-sugar product

5T67 の概要

• エントリーDOI: 10.2210/pdb5t67/pdb
• 関連するPDBエントリー: 5T6B 5t64
• 分子名称: Sugar 3-C-methyl transferase, ZINC ION, S-ADENOSYL-L-HOMOCYSTEINE, ... (8 entities in total)
• 機能のキーワード: c3-methyltransferase, antitumor, antibiotic, kijanimicin, transferase
• 由来する生物種: Actinomadura kijaniata
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 93978.00

構造登録者

Holden, H.M.,Thoden, J.B.,Dow, G.T. (登録日: 2016-09-01, 公開日: 2016-09-14, 最終更新日: 2023-10-04)

主引用文献

Dow, G.T.,Thoden, J.B.,Holden, H.M.
Structural studies on KijD1, a sugar C-3'-methyltransferase.
Protein Sci., 25:2282-2289, 2016

PubMed Abstract: Kijanimicin is an antitumor antibiotic isolated from Actinomadura kijaniata. It is composed of three distinct moieties: a pentacyclic core, a monosaccharide referred to as d-kijanose, and a tetrasaccharide chain composed of l-digitoxose units. d-Kijanose is a highly unusual nitro-containing tetradeoxysugar, which requires at least ten enzymes for its production. Here we describe a structural analysis of one of these enzymes, namely KijD1, which functions as a C-3'-methyltransferase using S-adenosylmethionine as its cofactor. For this investigation, two ternary complexes of KijD1, determined in the presence of S-adenosylhomocysteine (SAH) and dTDP or SAH and dTDP-3-amino-2,3,6-trideoxy-4-keto-3-methyl-d-glucose, were solved to 1.7 or 1.6 Å resolution, respectively. Unexpectedly, these structures, as well as additional biochemical analyses, demonstrated that the quaternary structure of KijD1 is a dimer. Indeed, this is in sharp contrast to that previously observed for the sugar C-3'-methyltransferase isolated from Micromonospora chalcea. By the judicious use of site-directed mutagenesis, it was possible to convert the dimeric form of KijD1 into a monomeric version. The quaternary structure of KijD1 could not have been deduced based solely on bioinformatics approaches, and thus this investigation highlights the continuing need for experimental validation.

PubMed: 27595766
DOI: 10.1002/pro.3034

実験手法

X-RAY DIFFRACTION (1.6 Å)