3wg5
1510-N membrane-bound stomatin-specific protease K138A mutant in complex with a substrate peptide under heat treatment1510-N membrane-bound stomatin-specific protease K138A mutant in complex with a substrate peptide under heat treatment
Structural highlights
FunctionSTOPP_PYRHO Protease that cleaves its substrates preferentially near hydrophobic or aromatic amino acid residues. Can degrade casein and the stomatin homolog PH1511 (in vitro).[1] [2] [3] Publication Abstract from PubMedMembrane-bound proteases are involved in various regulatory functions. The N-terminal region of PH1510p (1510-N) from the hyperthermophilic archaeon Pyrococcus horikoshii is a serine protease with a catalytic Ser-Lys dyad (Ser97 and Lys138), and specifically cleaves the C-terminal hydrophobic region of the p-stomatin PH1511p. In a form of human hemolytic anemia known as hereditary stomatocytosis, the stomatin protein is deficient in the erythrocyte membrane due to mis-trafficking. In order to understand the catalytic mechanism of 1510-N in more detail, here the structural and biochemical analysis of 1510-N is reported. Two degraded products were produced via acyl-enzyme intermediates. 1510-N is a thermostable protease, and thus crystallization after heat treatment of the protease-peptide complex was attempted in order to understand the catalytic mechanism of 1510-N. The structure after heat treatment is almost identical to that with no heat treatment. According to the superposition between the structures with heat treatment and with no heat treatment, the N-terminal half of the peptide is superposed well, whereas the C-terminal half of the peptide is slightly deviated. The N-terminal half of the peptide binds to 1510-N more tightly than the C-terminal half of the peptide. The flexible L2 loops of 1510-N cover the peptide, and are involved in the protease activity. Structural and biochemical analysis of a thermostable membrane-bound stomatin-specific protease.,Yokoyama H, Kobayashi D, Takizawa N, Fujii S, Matsui I J Synchrotron Radiat. 2013 Nov;20(Pt 6):933-7. doi: 10.1107/S0909049513021328., Epub 2013 Sep 25. PMID:24121343[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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