4DOT

Crystal structure of human HRASLS3.

4DOT の概要

• エントリーDOI: 10.2210/pdb4dot/pdb
• 分子名称: Group XVI phospholipase A2 (2 entities in total)
• 機能のキーワード: alpha/beta fold, phospholipase/acyltransferase, phosphatidylcholine, phosphatidylethanolamine, membrane, hydrolase
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cytoplasm: P53816
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 15896.98

構造登録者

Kiser, P.D.,Golczak, M.,Sears, A.E.,Lodowski, D.T.,Palczewski, K. (登録日: 2012-02-10, 公開日: 2012-05-30, 最終更新日: 2024-02-28)

主引用文献

Golczak, M.,Kiser, P.D.,Sears, A.E.,Lodowski, D.T.,Blaner, W.S.,Palczewski, K.
Structural Basis for the Acyltransferase Activity of Lecithin:Retinol Acyltransferase-like Proteins.
J.Biol.Chem., 287:23790-23807, 2012

PubMed Abstract: Lecithin:retinol acyltransferase-like proteins, also referred to as HRAS-like tumor suppressors, comprise a vertebrate subfamily of papain-like or NlpC/P60 thiol proteases that function as phospholipid-metabolizing enzymes. HRAS-like tumor suppressor 3, a representative member of this group, plays a key role in regulating triglyceride accumulation and energy expenditure in adipocytes and therefore constitutes a novel pharmacological target for treatment of metabolic disorders causing obesity. Here, we delineate a catalytic mechanism common to lecithin:retinol acyltransferase-like proteins and provide evidence for their alternative robust lipid-dependent acyltransferase enzymatic activity. We also determined high resolution crystal structures of HRAS-like tumor suppressor 2 and 3 to gain insight into their active site architecture. Based on this structural analysis, two conformational states of the catalytic Cys-113 were identified that differ in reactivity and thus could define the catalytic properties of these two proteins. Finally, these structures provide a model for the topology of these enzymes and allow identification of the protein-lipid bilayer interface. This study contributes to the enzymatic and structural understanding of HRAS-like tumor suppressor enzymes.

PubMed: 22605381
DOI: 10.1074/jbc.M112.361550

実験手法

X-RAY DIFFRACTION (1.96 Å)