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A251E
the mutant shows increased activity compared to the wild type cathepsin A
K355Q
the mutant shows increased activity compared to the wild type cathepsin A
L354D
the mutant shows decreased activity compared to the wild type cathepsin A
P451A
the mutant shows increased activity compared to the wild type cathepsin A
R20A
the mutant shows decreased activity compared to the wild type cathepsin A
R262A/R292A
double mutant also undergoes processing to form large and small subunits, suggesting alternative avenues for the maturation of cathepsin A
R344A
the mutant shows about wild type cathepsin A activity
R344D
inactive mutant, the 54 kDa precursor/zymogen with the R344D substitution is not processed to the 32/20 kDa mature form with CathA activity
R344E
the mutant shows reduced cathepsin A activity compared to the wild type
R344G
the mutant shows reduced cathepsin A activity compared to the wild type
R344I
the mutant shows reduced cathepsin A activity compared to the wild type
R344K
the mutant shows reduced cathepsin A activity compared to the wild type
R344M
the mutant shows reduced cathepsin A activity compared to the wild type
R344N
the mutant shows reduced cathepsin A activity compared to the wild type
R344P
the mutant shows reduced cathepsin A activity compared to the wild type
R344Q
the mutant shows reduced cathepsin A activity compared to the wild type
R344S
the mutant shows about wild type cathepsin A activity
R344V
the mutant shows reduced cathepsin A activity compared to the wild type
S150A/R284A/R298A
triple mutant S150A/R284A/R298A also undergoes cleavage into large and small subunits, comparable with the wildtype cathepsin A, suggesting that these sites are not mandatory for the activation of cathepsin A
W382A
the mutant shows decreased activity compared to the wild type cathepsin A
T343F
-
the mutant accumulates in the microsomal fraction of protoplasts treated with 2-mercaptoethanol and is for the most part susceptible to digestion by endoglycosidase H
C341F
-
reduced ratio of turnover number to Km-value for the mutant enzyme compared to wild-type enzyme with the substrates benzyloxycarbonyl-Gly-Leu, benzyloxycarbonyl-Phe-Leu, benzyloxycarbonyl-Gly-Phe and benzyloxycarbonyl-Ala-Phe
C341G
-
reduced ratio of turnover number to Km-value for the mutant enzyme compared to wild-type enzyme with the substrates benzyloxycarbonyl-Gly-Leu, benzyloxycarbonyl-Phe-Leu and benzyloxycarbonyl-Gly-Phe, somewhat increased ratio with benzyloxycarbonyl-Ala-Phe
C341S
-
reduced ratio of turnover number to Km-value for the mutant enzyme compared to wild-type enzyme with the substrates benzyloxycarbonyl-Gly-Leu, benzyloxycarbonyl-Phe-Leu, benzyloxycarbonyl-Gly-Phe and benzyloxycarbonyl-Ala-Phe
C341V
-
reduced ratio of turnover number to Km-value for the mutant enzyme compared to wild-type enzyme with the substrates benzyloxycarbonyl-Gly-Leu, benzyloxycarbonyl-Phe-Leu, benzyloxycarbonyl-Gly-Phe and benzyloxycarbonyl-Ala-Phe
E355Q
-
mutant shows moderate CPY secretion
E365A
-
mutant shows moderate CPY secretion
E369A
-
mutant shows moderate CPY secretion
E371A
-
mutant shows CPY secretion similar to the wild type
G255R
-
PNGase releases N-glycans from the mutant during the endoplasmic reticulum-associated degradation process in vivo. A major endoproteolytic reaction on the mutant appears to occur between amino acid 400 and 404
L267A
-
kcat/Km of mutant enzyme in% of the of the wild-type value: 18.7% for furylacryloyl-Ala-Leu, 71.7% for furylacryloyl-Ala-Glu, 113% for furylacryloyl-Ala-Lys, 130% for furylacryloyl-Ala-Arg,10.8% for furylacryloyl-Phe-Ala, 18.5% for furylacryloyl-Phe-Val and 31.3% for furylacryloyl-Phe-Leu
L267D
-
mutation greatly reduces the activity towards hydrophobic P1' residues and increases the activity for the hydrolysis of substrates with Lys or Arg in P1'
L267D/L272D
-
mutant enzyme with a preference for substrates with C-terminal basic amino acid residues
L267E
-
mutation greatly reduces the activity towards hydrophobic P1' residues and increases the activity for the hydrolysis of substrates with Lys or Arg in P1'
L267F
-
kcat/Km of mutant enzyme in% of the of the wild-type value: 88.5% for furylacryloyl-Ala-Leu, 65.2% for furylacryloyl-Ala-Glu, 44% for furylacryloyl-Ala-Lys, 53% for furylacryloyl-Ala-Arg, 34.2% for furylacryloyl-Phe-Ala, 57.8% for furylacryloyl-Phe-Val and 82.6% for furylacryloyl-Phe-Leu
L267K
-
mutation does not increase the rather low activity towards substrates with Glu in the P1' position but greatly reduces the activity towards substrates with C-terminal Lys or Arg due to electrostatic repulsion
L267Q
-
kcat/Km of mutant enzyme in% of the of the wild-type value: 17% for furylacryloyl-Ala-Leu, 48% for furylacryloyl-Ala-Glu, 157% for furylacryloyl-Ala-Lys, 63% for furylacryloyl-Ala-Arg
L267R
-
mutation does not increase the rather low activity towards substrates with Glu in the P1' position but greatly reduces the activity towards substrates with C-terminal Lys or Arg due to electrostatic repulsion
L272A
-
kcat/Km of mutant enzyme in% of the of the wild-type value: 8.7% for furylacryloyl-Ala-Leu, 60.9% for furylacryloyl-Ala-Glu, 127% for furylacryloyl-Ala-Lys, 47% for furylacryloyl-Ala-Arg, 78.9% for furylacryloyl-Phe-Ala, 50% for furylacryloyl-Phe-Val and 15.6% for furylacryloyl-Phe-Leu
L272F
-
kcat/Km of mutant enzyme in% of the of the wild-type value: 83% for furylacryloyl-Ala-Leu, 95.7% for furylacryloyl-Ala-Glu, 46% for furylacryloyl-Ala-Lys, 63% for furylacryloyl-Ala-Arg, 113% for furylacryloyl-Phe-Ala, 121% for furylacryloyl-Phe-Val and 83.4% for furylacryloyl-Phe-Leu
L272K
-
mutation does not increase the rather low activity towards substrates with Glu in the P1' position but greatly reduces the activity towards substrates with C-terminal Lys or Arg due to electrostatic repulsion
L272R
-
mutation does not increase the rather low activity towards substrates with Glu in the P1' position but greatly reduces the activity towards substrates with C-terminal Lys or Arg due to electrostatic repulsion
N356A
-
mutant shows CPY secretion similar to the wild type
N87I
-
mutant enzyme with reduced transport rate and reduced enzymatic activity, 30%
S297A
-
kcat/Km of mutant enzyme in% of the of the wild-type value: 39.7% for furylacryloyl-Ala-Leu, 161% for furylacryloyl-Ala-Glu, 66% for furylacryloyl-Ala-Lys, 80% for furylacryloyl-Ala-Arg, 126% for furylacryloyl-Phe-Ala, 109% for furylacryloyl-Phe-Val and 88.6% for furylacryloyl-Phe-Leu
S297F
-
kcat/Km of mutant enzyme in% of the of the wild-type value: 43.7% for furylacryloyl-Ala-Leu, 71.7% for furylacryloyl-Ala-Glu, 42% for furylacryloyl-Ala-Lys, 6.7% for furylacryloyl-Ala-Arg, 86.8% for furylacryloyl-Phe-Ala, 55% for furylacryloyl-Phe-Val and 60.9% for furylacryloyl-Phe-Leu
S297K
-
mutation does not increase the rather low activity towards substrates with Glu in the P1' position but greatly reduces the activity towards substrates with C-terminal Lys or Arg due to electrostatic repulsion
S297R
-
mutation does not increase the rather low activity towards substrates with Glu in the P1' position but greatly reduces the activity towards substrates with C-terminal Lys or Arg due to electrostatic repulsion
nutrition
-
the enzyme can be used to eliminate the bitterness of bitter peptides
L267D/L272A
-
-
L267D/L272A
-
kcat/Km of mutant enzyme in% of the of the wild-type value: 1.2% for furylacryloyl-Ala-Leu, 13% for furylacryloyl-Ala-Glu, 423% for furylacryloyl-Ala-Lys, 70% for furylacryloyl-Ala-Arg
L272D
-
-
L272D
-
kcat/Km of mutant enzyme in% of the of the wild-type value: 10.4% for furylacryloyl-Ala-Leu, 67% for furylacryloyl-Ala-Glu, 61.9% for furylacryloyl-Ala-Lys, 26% for furylacryloyl-Ala-Arg
L272E
-
-
L272E
-
kcat/Km of mutant enzyme in% of the of the wild-type value: 4% for furylacryloyl-Ala-Leu, 30% for furylacryloyl-Ala-Glu, 257% for furylacryloyl-Ala-Lys, 70% for furylacryloyl-Ala-Arg
L272Q
-
-
L272Q
-
kcat/Km of mutant enzyme in% of the of the wild-type value: 3.3% for furylacryloyl-Ala-Leu, 70% for furylacryloyl-Ala-Glu, 87% for furylacryloyl-Ala-Lys, 32% for furylacryloyl-Ala-Arg
L272R/M398F
-
-
L272R/M398F
-
kcat/Km of mutant enzyme in% of the of the wild-type value: 6.3% for furylacryloyl-Ala-Leu, 176% for furylacryloyl-Ala-Glu, 0.3% for furylacryloyl-Ala-Lys, 0.2% for furylacryloyl-Ala-Arg
L272R/T60F
-
-
L272R/T60F
-
kcat/Km of mutant enzyme in% of the of the wild-type value: 60% for furylacryloyl-Ala-Leu, 172% for furylacryloyl-Ala-Glu, 2.8% for furylacryloyl-Ala-Lys, 2.1% for furylacryloyl-Ala-Arg
S297D
-
-
S297D
-
kcat/Km of mutant enzyme in% of the of the wild-type value: 39.6% for furylacryloyl-Ala-Leu, 72% for furylacryloyl-Ala-Glu, 73% for furylacryloyl-Ala-Lys, 25% for furylacryloyl-Ala-Arg
S297E
-
-
S297E
-
kcat/Km of mutant enzyme in% of the of the wild-type value: 27% for furylacryloyl-Ala-Leu, 63% for furylacryloyl-Ala-Glu, 58% for furylacryloyl-Ala-Lys, 24% for furylacryloyl-Ala-Arg
S297Q
-
-
S297Q
-
kcat/Km of mutant enzyme in% of the of the wild-type value: 25% for furylacryloyl-Ala-Leu, 80% for furylacryloyl-Ala-Glu, 41% for furylacryloyl-Ala-Lys, 19.3% for furylacryloyl-Ala-Arg
T60F/L267D/L272A
-
-
T60F/L267D/L272A
-
kcat/Km of mutant enzyme in% of the of the wildtype value: 6% for furylacryloyl-Ala-Leu, 80% for furylacryloyl-Ala-Glu, 789% for furylacryloyl-Ala-Lys, 280% for furylacryloyl-Ala-Arg
additional information
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the gene vps4 null mutant missorts the vacuolar enzyme carboxypeptidase Y
additional information
a yeast two-hybrid screening using a cDNA library of osteoclast precursors discloses PPCA as a binding partner of NF-kappaB p50/p65. Forced expression of PPCA with p50/p65 in HEK293 cells decreases both the level of p50/p65 proteins and the transcriptional activity. Overexpression of PPCA causes the disappearance of p50/p65 in both the lysosomal and cytosolic fractions. PPCA is expressed throughout osteoclastogenesis,and the expression is slightly up-regulated by nuclear factor (NF)-kappaB ligand signaling. Knockdown of PPCA in osteoclast precursors with PPCA siRNA stimulates binding of nuclear proteins to oligonucleotides containing an NF-kappaB binding motif and increases osteoclastogenesis
additional information
-
carboxypeptidase Y is partially missorted to the cell surface in certain mutants of the COPIB subcomplex (COPIb, Sec27, Sec28, and possibly Sec33), which indicates an impairment in endosomal transport
additional information
-
the gene vps4 null mutant missorts the vacuolar enzyme carboxypeptidase Y
additional information
-
three signal sequences of Saccharomyces cerevisiae mating factor a (MFalpha) and invertase (SUC2), and Kluyveromyces marxianus inulinase (INU1) are combined with proCPY to increase a transporting efficiency from the endoplasmic reticulum in Saccharomyces cerevisiae. The MFalpha signal sequence gives the best specific activity of extracellular CPY