4DOT

Crystal structure of human HRASLS3.

Summary for 4DOT

• Entry DOI: 10.2210/pdb4dot/pdb
• Descriptor: Group XVI phospholipase A2 (2 entities in total)
• Functional Keywords: alpha/beta fold, phospholipase/acyltransferase, phosphatidylcholine, phosphatidylethanolamine, membrane, hydrolase
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm: P53816
• Total number of polymer chains: 1
• Total formula weight: 15896.98

Authors

Kiser, P.D.,Golczak, M.,Sears, A.E.,Lodowski, D.T.,Palczewski, K. (deposition date: 2012-02-10, release date: 2012-05-30, Last modification date: 2024-02-28)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (1.96 Å)