2XB8

Structure of Mycobacterium tuberculosis type II dehydroquinase in complex with inhibitor compound (2R)-2-(4-methoxybenzyl)-3- dehydroquinic acid

2XB8 の概要

• エントリーDOI: 10.2210/pdb2xb8/pdb
• 関連するPDBエントリー: 1H05 1H0R 1H0S 2DHQ 2XB9
• 分子名称: 3-DEHYDROQUINATE DEHYDRATASE, (1R,2R,4S,5R)-1,4,5-TRIHYDROXY-2-(4-METHOXYBENZYL)-3-OXOCYCLOHEXANECARBOXYLIC ACID, SULFATE ION, ... (5 entities in total)
• 機能のキーワード: lyase, amino acid biosynthesis
• 由来する生物種: MYCOBACTERIUM TUBERCULOSIS
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 16781.62

構造登録者

Otero, J.M.,Tizon, L.,Llamas-Saiz, A.L.,Fox, G.C.,Gonzalez-Bello, C.,van Raaij, M.J. (登録日: 2010-04-08, 公開日: 2010-09-15, 最終更新日: 2023-12-20)

主引用文献

Peon, A.,Otero, J.M.,Tizon, L.,Prazeres, V.F.V.,Llamas-Saiz, A.L.,Fox, G.C.,van Raaij, M.J.,Lamb, H.,Hawkins, A.R.,Gago, F.,Castedo, L.,Gonzalez-Bello, C.
Understanding the Key Factors that Control the Inhibition of Type II Dehydroquinase by (2R)-2- Benzyl-3-Dehydroquinic Acids.
Chemmedchem, 5:1726-, 2010

PubMed Abstract: The binding mode of several substrate analogues, (2R)-2-benzyl-3-dehydroquinic acids 4, which are potent reversible competitive inhibitors of type II dehydroquinase (DHQ2), the third enzyme of the shikimic acid pathway, has been investigated by structural and computational studies. The crystal structures of Mycobacterium tuberculosis and Helicobacter pylori DHQ2 in complex with one of the most potent inhibitor, p-methoxybenzyl derivative 4 a, have been solved at 2.40 Å and 2.75 Å, respectively. This has allowed the resolution of the M. tuberculosis DHQ2 loop containing residues 20-25 for the first time. These structures show the key interactions of the aromatic ring in the active site of both enzymes and additionally reveal an important change in the conformation and flexibility of the loop that closes over substrate binding. The loop conformation and the binding mode of compounds 4 b-d has been also studied by molecular dynamics simulations, which suggest that the benzyl group of inhibitors 4 prevent appropriate orientation of the catalytic tyrosine of the loop for proton abstraction and disrupts its basicity.

PubMed: 20815012
DOI: 10.1002/CMDC.201000281

実験手法

X-RAY DIFFRACTION (2.4 Å)