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Crystal structure of human HRASLS3.Crystal structure of human HRASLS3.
Structural highlights
Function[PAG16_HUMAN] Exhibits PLA1/2 activity, catalyzing the calcium-independent hydrolysis of acyl groups in various phosphatidylcholines (PC) and phosphatidylethanolamine (PE). For most substrates, PLA1 activity is much higher than PLA2 activity. Specifically catalyzes the release of fatty acids from phospholipids in adipose tissue (By similarity). N- and O-acylation activity is hardly detectable. Might decrease protein phosphatase 2A (PP2A) activity.[1] [2] Publication Abstract from PubMedLecithin: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. Structural Basis for the Acyltransferase Activity of Lecithin:Retinol Acyltransferase-like Proteins.,Golczak M, Kiser PD, Sears AE, Lodowski DT, Blaner WS, Palczewski K J Biol Chem. 2012 Jul 6;287(28):23790-807. Epub 2012 May 17. PMID:22605381[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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