Literature summary for 3.4.22.16 extracted from

Hao, Y.; Purtha, W.; Cortesio, C.; Rui, H.; Gu, Y.; Chen, H.; Sickmier, E.A.; Manzanillo, P.; Huang, X.
Crystal structures of human procathepsin H (2018), PLoS ONE, 13, e0200374 .

Search for more literature for 3.4.22.16

Activating Compound

Activating Compound	Comment	Organism	Structure
additional information	procathepsin H is not capable of autoactivation and requires other proteases such as cathepsin L for its activation	Homo sapiens

Cloned(Commentary)

Cloned (Comment)	Organism
procathepsin H (Ala1P-Val220) construct is cloned with an N-terminal gp64 secretion signal peptide and an uncleavable C-terminal His6-tag, recombinant expression of wild-type enzyme in Spodoptera frugiperda Sf9 cells using the baculovirus transfection system, recombinant expression of His-tagged mutant enzymes in HEK-293T cells using the lentiviral viral vector CD731B	Homo sapiens

Crystallization (Commentary)

Crystallization (Comment)	Organism
purified wild-type and C26S mutant procathepsin H, sitting drop vapor diffusion method, 5.7 mg/ml protein, crystal growth from 0.1 M Na2HPO4/citric acid, pH 4.2, and 2.0 M (NH4)2SO4, 1 week, 20°C, method optimization, X-ray diffraction structure determination and analysis at 2.0 A and 1.66 A resolution, respectively, molecular replacement and modeling	Homo sapiens

Protein Variants

Protein Variants	Comment	Organism
C26S	site-directed mutagenesis, catalytically inactive active site mutant	Homo sapiens
C80S	site-directed mutagenesis, the mutation removes the disulfide between the mini-chain and the mature domain and completely abolishes the protease activity	Homo sapiens
H166A	site-directed mutagenesis, catalytically inactive active site mutant	Homo sapiens
N186A	site-directed mutagenesis, catalytically inactive active site mutant	Homo sapiens
T83A	site-directed mutagenesis, mutation of the Thr83 of the mini-chain has only mild effects on the enzyme activity	Homo sapiens

General Stability

General Stability	Organism
analysis of stability of the mini-chain in cathepsin H and procathepsin H, overview	Homo sapiens

Inhibitors

Inhibitors	Comment	Organism	Structure
E64d	-	Homo sapiens
additional information	molecular basis for the inhibition of the mature enzyme by the prodomain. The prodomain of procathepsin H has an N-terminal helical subdomain (Ala1P-Ser75P) and an extended portion (Glu76P-Pro93P) that links the helical subdomain to Tyr1 of the mature domain	Homo sapiens

Localization

Localization	Comment	Organism	GeneOntology No.	Textmining
lysosome	-	Homo sapiens	5764	-

Organism

Organism	UniProt	Comment	Textmining
Homo sapiens	P09668	-	-

Posttranslational Modification

Posttranslational Modification	Comment	Organism
glycoprotein	the enzyme harbors two glycosylation sites, Asn79P on the mini-chain of the prodomain and Asn115 on the mature domain. No glycan is built for Asn79P in cathepsin H due to poor electron density, although it is glycosylated	Homo sapiens
proteolytic modification	the enzyme is synthesized as an inactive proenzyme, the N-terminal prodomain (Ala1P-Pro93P) is cleaved off for maturation, a C-terminal mature domain (Tyr1-Val220) with a disulfide bridge between Cys212 and the mini-chain Cys80P remains. Procathepsin H is not autoactivated but can be transactivated by cathepsin L. The prodomain of procathepsin H has an N-terminal helical subdomain (Ala1P-Ser75P) and an extended portion (Glu76P-Pro93P) that links the helical subdomain to Tyr1 of the mature domain	Homo sapiens

Purification (Commentary)

Purification (Comment)	Organism
recombinant His-tagged wild-type and mutant enzymes from Spodoptera frugiperda Sf9 cells or HEK-23T cells, respectively, by nickel affinity chromatography and gel filtration	Homo sapiens

Substrates and Products (Substrate)

Substrates	Comment Substrates	Organism	Products	Comment (Products)	Rev.	Reac.
Arg-7-amido-4-trifluoromethylcoumarin + H2O	fluorogenic cathepsin H substrate	Homo sapiens	Arg + 7-amino-4-trifluoromethylcoumarin	-	?
additional information	procathepsin H is not capable of autocleavage at pH 4.5-6.5	Homo sapiens	?	-	?

Synonyms

Synonyms	Comment	Organism
procathepsin H	-	Homo sapiens

General Information

General Information	Comment	Organism
evolution	cathepsin H is a member of the papain superfamily of lysosomal cysteine proteases	Homo sapiens
additional information	the catalytic triad residues Cys26, His166 and Asn186 of procathepsin H reside in the active site cleft	Homo sapiens
physiological function	the mature enzyme is inhibited by its own prodomain after maturation cleavage. Upon activation, cathepsin H displays a distinct proteolytic activity among the papain superfamily, functioning predominantly as an aminopeptidase that cleaves a single N-terminal residue from a polypeptide chain. Cathepsin H has also been shown to act as an endopeptidase, although with much lower efficiency	Homo sapiens

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Release 2023.1 (January 2023)