4ZEV

Crystal structure of PfHAD1 in complex with mannose-6-phosphate

4ZEV の概要

• エントリーDOI: 10.2210/pdb4zev/pdb
• 関連するPDBエントリー: 4ZEW 4ZEX
• 分子名称: PfHAD1, MAGNESIUM ION, 6-O-phosphono-alpha-D-mannopyranose, ... (5 entities in total)
• 機能のキーワード: c2 had, sugar phosphatase, haloacid-dehalogenase, mannose-6-phosphate, unknown function
• 由来する生物種: Plasmodium falciparum (isolate 3D7)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 68145.00

構造登録者

Park, J.,Tolia, N.H. (登録日: 2015-04-20, 公開日: 2015-09-09, 最終更新日: 2023-09-27)

主引用文献

Park, J.,Guggisberg, A.M.,Odom, A.R.,Tolia, N.H.
Cap-domain closure enables diverse substrate recognition by the C2-type haloacid dehalogenase-like sugar phosphatase Plasmodium falciparum HAD1.
Acta Crystallogr. D Biol. Crystallogr., 71:1824-1834, 2015

PubMed Abstract: Haloacid dehalogenases (HADs) are a large enzyme superfamily of more than 500,000 members with roles in numerous metabolic pathways. Plasmodium falciparum HAD1 (PfHAD1) is a sugar phosphatase that regulates the methylerythritol phosphate (MEP) pathway for isoprenoid synthesis in malaria parasites. However, the structural determinants for diverse substrate recognition by HADs are unknown. Here, crystal structures were determined of PfHAD1 in complex with three sugar phosphates selected from a panel of diverse substrates that it utilizes. Cap-open and cap-closed conformations are observed, with cap closure facilitating substrate binding and ordering. These structural changes define the role of cap movement within the major subcategory of C2 HAD enzymes. The structures of an HAD bound to multiple substrates identifies binding and specificity-determining residues that define the structural basis for substrate recognition and catalysis within the HAD superfamily. While the substrate-binding region of the cap domain is flexible in the open conformations, this region becomes ordered and makes direct interactions with the substrate in the closed conformations. These studies further inform the structural and biochemical basis for catalysis within a large superfamily of HAD enzymes with diverse functions.

PubMed: 26327372
DOI: 10.1107/S1399004715012067

実験手法

X-RAY DIFFRACTION (1.8 Å)