Novel dimer structure of a membrane-bound protease with a catalytic Ser-Lys dyad and its linkage to stomatin.
Membrane-bound proteases are involved in various regulatory functions. A previous report indicates that the N-terminal region of PH1510 (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 PH1511. According to the crystal structure of the wild-type 1510-N in dimeric form, the active site around Ser97 is in a hydrophobic environment suitable for the hydrophobic substrates. This article reports the crystal structure of the K138A mutant of 1510-N at 2.3 A resolution. The determined structure contains one molecule per asymmetric unit, but 1510-N is active in dimeric form. Two possible sets of dimer were found from the symmetry-related molecules. One dimer is almost the same as the wild-type 1510-N. Another dimer is probably in an inactive form. The L2 loop, which is disordered in the wild-type structure, is significantly kinked at around A-138 in the K138A mutant. Thus Lys138 probably has an important role on the conformation of L2.
Yokoyama
Hideshi
H
School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka 422-8526, Japan.
Hamamatsu
Shiho
S
Fujii
Satoshi
S
Matsui
Ikuo
I
D000595:Amino Acid Sequence; D019843:Archaeal Proteins / Q000737:chemistry / Q000378:metabolism*; D002384:Catalysis; D019281:Dimerization; D008239:Lysine / Q000737:chemistry*; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism*; D008969:Molecular Sequence Data; D011487:Protein Conformation; D043902:Pyrococcus horikoshii / Q000201:enzymology*; D012694:Serine / Q000737:chemistry*; D012697:Serine Endopeptidases / Q000737:chemistry / Q000378:metabolism*
D019843:Archaeal Proteins; D008565:Membrane Proteins; D012694:Serine; D012697:Serine Endopeptidases; D008239:Lysine