5CKX

Non-covalent complex of DAHP synthase and chorismate mutase from Mycobacterium tuberculosis with bound transition state analog and feedback effectors tyrosine and phenylalanine

5CKX の概要

• エントリーDOI: 10.2210/pdb5ckx/pdb
• 分子名称: Phospho-2-dehydro-3-deoxyheptonate aldolase AroG, Intracellular chorismate mutase, MANGANESE (II) ION, ... (10 entities in total)
• 機能のキーワード: protein complex, shikimate pathway, dahp-synthase, chorismate mutase, transferase-isomerase complex, transferase/isomerase
• 由来する生物種: Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv); 詳細
• 細胞内の位置: Cytoplasm : P9WIC1
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 126411.89

構造登録者

Munack, S.,Okvist, M.,Krengel, U. (登録日: 2015-07-15, 公開日: 2016-03-16, 最終更新日: 2024-01-10)

主引用文献

Munack, S.,Roderer, K.,Okvist, M.,Kamarauskaite, J.,Sasso, S.,van Eerde, A.,Kast, P.,Krengel, U.
Remote Control by Inter-Enzyme Allostery: A Novel Paradigm for Regulation of the Shikimate Pathway.
J.Mol.Biol., 428:1237-1255, 2016

PubMed Abstract: DAHP synthase and chorismate mutase catalyze key steps in the shikimate biosynthetic pathway en route to aromatic amino acids. In Mycobacterium tuberculosis, chorismate mutase (MtCM; Rv0948c), located at the branch point toward phenylalanine and tyrosine, has poor activity on its own. However, it is efficiently activated by the first enzyme of the pathway, DAHP synthase (MtDS; Rv2178c), through formation of a non-covalent MtCM-MtDS complex. Here, we show how MtDS serves as an allosteric platform for feedback regulation of both enzymes, using X-ray crystallography, small-angle X-ray scattering, size-exclusion chromatography, and multi-angle light scattering. Crystal structures of the fully inhibited MtDS and the allosterically down-regulated MtCM-MtDS complex, solved at 2.8 and 2.7Å, respectively, reveal how effector binding at the internal MtDS subunit interfaces regulates the activity of MtDS and MtCM. While binding of all three metabolic end products to MtDS shuts down the entire pathway, the binding of phenylalanine jointly with tyrosine releases MtCM from the MtCM-MtDS complex, hence suppressing MtCM activation by 'inter-enzyme allostery'. This elegant regulatory principle, invoking a transient allosteric enzyme interaction, seems to be driven by dynamics and is likely a general strategy used by nature.

PubMed: 26776476
DOI: 10.1016/j.jmb.2016.01.001

実験手法

X-RAY DIFFRACTION (2.7 Å)