7OZM

Crystal Structure of mtbMGL K74A (Closed Cap Conformation)

7OZM の概要

• エントリーDOI: 10.2210/pdb7ozm/pdb
• 分子名称: Monoacylglycerol lipase, ISOPROPYL ALCOHOL (3 entities in total)
• 機能のキーワード: mycobacterium tuberculosis, monoacylglycerol lipase, hydrolase
• 由来する生物種: Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 33678.14

構造登録者

Grininger, C.,Aschauer, P.,Pavkov-Keller, T.,Oberer, M. (登録日: 2021-06-28, 公開日: 2021-09-15, 最終更新日: 2024-01-31)

主引用文献

Grininger, C.,Leypold, M.,Aschauer, P.,Pavkov-Keller, T.,Riegler-Berket, L.,Breinbauer, R.,Oberer, M.
Structural Changes in the Cap of Rv0183/mtbMGL Modulate the Shape of the Binding Pocket.
Biomolecules, 11:-, 2021

PubMed Abstract: Tuberculosis continues to be a major threat to the human population. Global efforts to eradicate the disease are ongoing but are hampered by the increasing occurrence of multidrug-resistant strains of . Therefore, the development of new treatment, and the exploration of new druggable targets and treatment strategies, are of high importance. Rv0183/mtbMGL, is a monoacylglycerol lipase of and it is involved in providing fatty acids and glycerol as building blocks and as an energy source. Since the lipase is expressed during the dormant and active phase of an infection, Rv0183/mtbMGL is an interesting target for inhibition. In this work, we determined the crystal structures of a surface-entropy reduced variant K74A Rv0183/mtbMGL in its free form and in complex with a substrate mimicking inhibitor. The two structures reveal conformational changes in the cap region that forms a major part of the substrate/inhibitor binding region. We present a completely closed conformation in the free form and semi-closed conformation in the ligand-bound form. These conformations differ from the previously published, completely open conformation of Rv0183/mtbMGL. Thus, this work demonstrates the high conformational plasticity of the cap from open to closed conformations and provides useful insights into changes in the substrate-binding pocket, the target of potential small-molecule inhibitors.

PubMed: 34572512
DOI: 10.3390/biom11091299

実験手法

X-RAY DIFFRACTION (2.15 Å)