4BC7

MAMMALIAN ALKYLDIHYDROXYACETONEPHOSPHATE SYNTHASE: Arg419His mutant

4BC7 の概要

• エントリーDOI: 10.2210/pdb4bc7/pdb
• 関連するPDBエントリー: 4BBY 4BC9 4BCA
• 分子名称: ALKYLDIHYDROXYACETONEPHOSPHATE SYNTHASE, PEROXISOMAL, FLAVIN-ADENINE DINUCLEOTIDE, SULFATE ION, ... (5 entities in total)
• 機能のキーワード: transferase, plasmalogen, flavin, peroxisome
• 由来する生物種: CAVIA PORCELLUS (GUINEA PIG)
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 295385.59

構造登録者

Nenci, S.,Piano, V.,Rosati, S.,Aliverti, A.,Pandini, V.,Fraaije, M.W.,Heck, A.J.R.,Edmondson, D.E.,Mattevi, A. (登録日: 2012-10-01, 公開日: 2012-11-07, 最終更新日: 2023-12-20)

主引用文献

Nenci, S.,Piano, V.,Rosati, S.,Aliverti, A.,Pandini, V.,Fraaije, M.W.,Heck, A.J.R.,Edmondson, D.E.,Mattevi, A.
Precursor of Ether Phospholipids is Synthesized by a Flavoenzyme Through Covalent Catalysis.
Proc.Natl.Acad.Sci.USA, 109:18791-, 2012

PubMed Abstract: The precursor of the essential ether phospholipids is synthesized by a peroxisomal enzyme that uses a flavin cofactor to catalyze a reaction that does not alter the redox state of the substrates. The enzyme crystal structure reveals a V-shaped active site with a narrow constriction in front of the prosthetic group. Mutations causing inborn ether phospholipid deficiency, a very severe genetic disease, target residues that are part of the catalytic center. Biochemical analysis using substrate and flavin analogs, absorbance spectroscopy, mutagenesis, and mass spectrometry provide compelling evidence supporting an unusual mechanism of covalent catalysis. The flavin functions as a chemical trap that promotes exchange of an acyl with an alkyl group, generating the characteristic ether bond. Structural comparisons show that the covalent versus noncovalent mechanistic distinction in flavoenzyme catalysis and evolution relies on subtle factors rather than on gross modifications of the cofactor environment.

PubMed: 23112191
DOI: 10.1073/PNAS.1215128109

実験手法

X-RAY DIFFRACTION (2.4 Å)