1HOX

CRYSTAL STRUCTURE OF RABBIT PHOSPHOGLUCOSE ISOMERASE COMPLEXED WITH FRUCTOSE-6-PHOSPHATE

1HOX の概要

• エントリーDOI: 10.2210/pdb1hox/pdb
• 関連するPDBエントリー: 1BOZ 1DQR 1G98 1HM5 1PGI 2PGI
• 分子名称: PHOSPHOGLUCOSE ISOMERASE, 6-O-phosphono-beta-D-fructofuranose (3 entities in total)
• 機能のキーワード: emzyme -substrate complex, isomerase
• 由来する生物種: Oryctolagus cuniculus (rabbit)
• 細胞内の位置: Cytoplasm: Q9N1E2
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 126175.51

構造登録者

Jeffrey, C.J.,Lee, J.H.,Chang, K.Z.,Patel, V. (登録日: 2000-12-11, 公開日: 2001-07-20, 最終更新日: 2023-08-09)

主引用文献

Lee, J.H.,Chang, K.Z.,Patel, V.,Jeffery, C.J.
Crystal structure of rabbit phosphoglucose isomerase complexed with its substrate D-fructose 6-phosphate.
Biochemistry, 40:7799-7805, 2001

PubMed Abstract: Phosphoglucose isomerase (PGI, EC 5.3.1.9) catalyzes the interconversion of D-glucose 6-phosphate (G6P) and D-fructose 6-phosphate (F6P) and plays important roles in glycolysis and gluconeogenesis. Biochemical characterization of the enzyme has led to a proposed multistep catalytic mechanism. First, the enzyme catalyzes ring opening to yield the open chain form of the substrate. Then isomerization proceeds via proton transfer between C2 and C1 of a cis-enediol(ate) intermediate to yield the open chain form of the product. Catalysis proceeds in both the G6P to F6P and F6P to G6P directions, so both G6P and F6P are substrates. X-ray crystal structure analysis of rabbit and bacterial PGI has previously identified the location of the enzyme active site, and a recent crystal structure of rabbit PGI identified Glu357 as a candidate functional group for transferring the proton. However, it was not clear which active site amino acid residues catalyze the ring opening step. In this paper, we report the X-ray crystal structure of rabbit PGI complexed with the cyclic form of its substrate, D-fructose 6-phosphate, at 2.1 A resolution. The location of the substrate relative to the side chains of His388 suggest that His388 promotes ring opening by protonating the ring oxygen. Glu216 helps to position His388, and a water molecule that is held in position by Lys518 and Thr214 accepts a proton from the hydroxyl group at C2. Comparison to a structure of rabbit PGI with 5PAA bound indicates that ring opening is followed by loss of the protonated water molecule and conformational changes in the substrate and the protein so that a helix containing amino acids 513-520 moves in toward the substrate to form additional hydrogen bonds with the substrate.

PubMed: 11425306
DOI: 10.1021/bi002916o

実験手法

X-RAY DIFFRACTION (2.1 Å)