The 1.4 a crystal structure of kumamolysin: a thermostable serine-carboxyl-type proteinase.
Kumamolysin is a thermostable endopeptidase from Bacillus novosp. MN-32, exhibiting maximal proteolytic activity around pH 3. It belongs to the newly identified family of serine-carboxyl proteinases, which also includes CLN2, a human lysosomal homolog recently implicated in a fatal neurodegenerative disease. Kumamolysin and its complexes with two aldehyde inhibitors were crystallized, and their three-dimensional structures were solved and refined with X-ray data to 1.4 A resolution. As its Pseudomonas homolog, kumamolysin exhibits a Ser/Glu/Asp catalytic triad with particularly short interconnecting hydrogen bonds and an oxyanion hole enabling the reactive serine to attack substrate peptide bonds at quite acidic pH. An additional Glu/Trp pair, unique to kumamolysin, might further facilitate proton delocalization during nucleophilic attack, in particular at high temperature.
Comellas-Bigler
Mireia
M
Abteilung für Strukturforschung, Max-Planck-Institut für Biochemie, Am Klopferspitz 18 a, D82152, Planegg-Martinsried, Germany.
Fuentes-Prior
Pablo
P
Maskos
Klaus
K
Huber
Robert
R
Oyama
Hiroshi
H
Uchida
Kenichi
K
Dunn
Ben M
BM
Oda
Kohei
K
Bode
Wolfram
W
D000595:Amino Acid Sequence; D016282:Aspartic Acid Endopeptidases / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D001407:Bacillus / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D001665:Binding Sites; D002118:Calcium / Q000378:metabolism; D018360:Crystallography, X-Ray; D006863:Hydrogen-Ion Concentration; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment; D020860:Subtilisin / Q000235:genetics; D000091346:Tripeptidyl-Peptidase 1
D000091346:Tripeptidyl-Peptidase 1; C000717267:TPP1 protein, human; D020860:Subtilisin; D016282:Aspartic Acid Endopeptidases; C078894:kumamolysin; D002118:Calcium