6qgn

Crystal structure of APT1 bound to 2-Bromopalmitate

spinqualitylabelsall models 6qgn, resolution 2.10Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6qgn is a 4 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.099Å Ligands: J1W Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function LYPA1_HUMAN Hydrolyzes fatty acids from S-acylated cysteine residues in proteins such as trimeric G alpha proteins or HRAS. Has depalmitoylating activity and also low lysophospholipase activity. Publication Abstract from PubMed Many biochemical reactions require controlled recruitment of proteins to membranes. This is largely regulated by posttranslational modifications. A frequent one is S-acylation, which consists of the addition of acyl chains and can be reversed by poorly understood acyl protein thioesterases (APTs). Using a panel of computational and experimental approaches, we dissect the mode of action of the major cellular thioesterase APT2 (LYPLA2). We show that soluble APT2 is vulnerable to proteasomal degradation, from which membrane binding protects it. Interaction with membranes requires three consecutive steps: electrostatic attraction, insertion of a hydrophobic loop and S-acylation by the palmitoyltransferases ZDHHC3 or ZDHHC7. Once bound, APT2 is predicted to deform the lipid bilayer to extract the acyl chain bound to its substrate and capture it in a hydrophobic pocket to allow hydrolysis. This molecular understanding of APT2 paves the way to understand the dynamics of APT2-mediated deacylation of substrates throughout the endomembrane system. Palmitoylated acyl protein thioesterase APT2 deforms membranes to extract substrate acyl chains.,Abrami L, Audagnotto M, Ho S, Marcaida MJ, Mesquita FS, Anwar MU, Sandoz PA, Fonti G, Pojer F, Dal Peraro M, van der Goot FG Nat Chem Biol. 2021 Apr;17(4):438-447. doi: 10.1038/s41589-021-00753-2. Epub 2021, Mar 11. PMID:33707782 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Thioesterase 3D structures

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