3DJ4

Crystal Structure of GlmU from Mycobacterium tuberculosis in complex with URIDINE-DIPHOSPHATE-N-ACETYLGLUCOSAMINE.

3DJ4 の概要

• エントリーDOI: 10.2210/pdb3dj4/pdb
• 関連するPDBエントリー: 3DIU
• 分子名称: Bifunctional protein glmU, MAGNESIUM ION, COBALT (II) ION, ... (5 entities in total)
• 機能のキーワード: acetyltransferase, bifunctional, pyrophosphorylase, rossmann-like fold, left-handed-beta-helix, trimer, cell shape, cell wall biogenesis/degradation, cytoplasm, magnesium, metal-binding, multifunctional enzyme, nucleotidyltransferase, peptidoglycan synthesis, transferase, acyltransferase
• 由来する生物種: Mycobacterium tuberculosis
• 細胞内の位置: Cytoplasm (By similarity): P96382
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 52328.32

構造登録者

Verma, S.K.,Prakash, B. (登録日: 2008-06-22, 公開日: 2009-05-19, 最終更新日: 2024-03-20)

主引用文献

Parikh, A.,Verma, S.K.,Khan, S.,Prakash, B.,Nandicoori, V.K.
PknB-mediated phosphorylation of a novel substrate, N-acetylglucosamine-1-phosphate uridyltransferase, modulates its acetyltransferase activity.
J.Mol.Biol., 386:451-464, 2009

PubMed Abstract: Identifying direct targets of kinases and determining how their activities are regulated are central to understanding how they generate biological responses. Genetic and biochemical studies have shown that Mycobacterium tuberculosis serine/threonine protein kinases PknA and PknB play a role in modulating cell shape and possibly cell division. In this report, we show that the enzyme N-acetylglucosamine-1-phosphate uridyltransferase (GlmU) of M. tuberculosis is a novel substrate of PknB and is phosphorylated on threonine residues. GlmU carries out two important biochemical activities: a C-terminal domain catalyzes the transfer of acetyl group from acetyl coenzyme A to glucosamine-1-phosphate to produce N-acetylglucosamine-1-phosphate, which is converted into UDP-N-acetylglucosamine by the transfer of uridine 5'-monophosphate (from uridine 5'-triphosphate), a reaction catalyzed by the N-terminal domain. We determined the crystal structures of GlmU in apo form and UDP-N-acetylglucosamine-bound form, and analyzed them to identify threonine residues that may be accessible to PknB. The structure shows a two-domain architecture, with an N-terminal domain having an alpha/beta-like fold and with a C-terminal domain that forms a left-handed parallel beta-helix structure. Kinase assays with PknB using the N- and C-terminal domains of GlmU as substrates illustrated that PknB phosphorylates GlmU in the C-terminal domain. Furthermore, mutational studies reveal one of the five threonines present in region 414-439 to be phosphorylated by PknB. Structural and biochemical analyses have shown the significance of a variable C-terminal tail in regulating acetyltransferase activity. Notably, we demonstrate that although PknB-mediated phosphorylation of GlmU does not affect its uridyltransferase activity, it significantly modulates the acetyltransferase activity. These findings imply a role for PknB in regulating peptidoglycan synthesis by modulating the acetyltransferase activity of GlmU.

PubMed: 19121323
DOI: 10.1016/j.jmb.2008.12.031

実験手法

X-RAY DIFFRACTION (2.38 Å)