2I55

Complex of glucose-1,6-bisphosphate with phosphomannomutase from Leishmania mexicana

2I55 の概要

• エントリーDOI: 10.2210/pdb2i55/pdb
• 関連するPDBエントリー: 2AMY 2FUC 2I54
• 分子名称: Phosphomannomutase, CHLORIDE ION, MAGNESIUM ION, ... (5 entities in total)
• 機能のキーワード: had domain, isomerase
• 由来する生物種: Leishmania mexicana
• 細胞内の位置: Cytoplasm : Q95ZD7
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 85219.72

構造登録者

Smith, B.J. (登録日: 2006-08-24, 公開日: 2007-04-17, 最終更新日: 2023-10-25)

主引用文献

Kedzierski, L.,Malby, R.L.,Smith, B.J.,Perugini, M.A.,Hodder, A.N.,Ilg, T.,Colman, P.M.,Handman, E.
Structure of Leishmania mexicana phosphomannomutase highlights similarities with human isoforms
J.Mol.Biol., 363:215-227, 2006

PubMed Abstract: Phosphomannomutase (PMM) catalyses the conversion of mannose-6-phosphate to mannose-1-phosphate, an essential step in mannose activation and the biosynthesis of glycoconjugates in all eukaryotes. Deletion of PMM from Leishmania mexicana results in loss of virulence, suggesting that PMM is a promising drug target for the development of anti-leishmanial inhibitors. We report the crystallization and structure determination to 2.1 A of L. mexicana PMM alone and in complex with glucose-1,6-bisphosphate to 2.9 A. PMM is a member of the haloacid dehalogenase (HAD) family, but has a novel dimeric structure and a distinct cap domain of unique topology. Although the structure is novel within the HAD family, the leishmanial enzyme shows a high degree of similarity with its human isoforms. We have generated L. major PMM knockouts, which are avirulent. We expressed the human pmm2 gene in the Leishmania PMM knockout, but despite the similarity between Leishmania and human PMM, expression of the human gene did not restore virulence. Similarities in the structure of the parasite enzyme and its human isoforms suggest that the development of parasite-selective inhibitors will not be an easy task.

PubMed: 16963079
DOI: 10.1016/j.jmb.2006.08.023

実験手法

X-RAY DIFFRACTION (2.9 Å)