2OI2

Streptococcus pneumoniae Mevalonate Kinase in Complex with Diphosphomevalonate

2OI2 の概要

• エントリーDOI: 10.2210/pdb2oi2/pdb
• 分子名称: Mevalonate kinase, MAGNESIUM ION, (3R)-3-HYDROXY-5-{[(R)-HYDROXY(PHOSPHONOOXY)PHOSPHORYL]OXY}-3-METHYLPENTANOIC ACID, ... (4 entities in total)
• 機能のキーワード: enzyme-inhibitor complex, transferase
• 由来する生物種: Streptococcus pneumoniae
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 31796.44

構造登録者

Andreassi, J.L.,Bilder, P.W.,Vetting, M.W.,Roderick, S.L.,Leyh, T.S. (登録日: 2007-01-10, 公開日: 2007-05-01, 最終更新日: 2023-12-27)

主引用文献

Andreassi, J.L.,Bilder, P.W.,Vetting, M.W.,Roderick, S.L.,Leyh, T.S.
Crystal structure of the Streptococcus pneumoniae mevalonate kinase in complex with diphosphomevalonate.
Protein Sci., 16:983-989, 2007

PubMed Abstract: Streptococcus pneumoniae, a ubiquitous gram-positive pathogen with an alarming, steadily evolving resistance to frontline antimicrobials, poses a severe global health threat both in the community and in the clinic. The recent discovery that diphosphomevalonate (DPM), an essential intermediate in the isoprenoid biosynthetic pathway, potently and allosterically inhibits S. pneumoniae mevalonate kinase (SpMK) without affecting the human isozyme established a new target and lead compound for antimicrobial design. Here we present the crystal structure of the first S. pneumoniae mevalonate kinase, at a resolution of 2.5 A and in complex with DPM.Mg(2+) in the active-site cleft. Structural comparison of SpMK with other members of the GHMP kinase family reveals that DPM functions as a partial bisubstrate analog (mevalonate linked to the pyrophosphoryl moiety of ATP) in that it elicits a ternary-complexlike form of the enzyme, except for localized disordering in a region that would otherwise interact with the missing portion of the nucleotide. Features of the SpMK-binding pockets are discussed in the context of established mechanistic findings and inherited human diseases linked to MK deficiency.

PubMed: 17400916
DOI: 10.1110/ps.072755707

実験手法

X-RAY DIFFRACTION (2.5 Å)