Circular zymogens of human ribonuclease 1.
HIV
circular protein
cytotoxin
intein
protease
ribonuclease
zymogen
Journal
Protein science : a publication of the Protein Society
ISSN: 1469-896X
Titre abrégé: Protein Sci
Pays: United States
ID NLM: 9211750
Informations de publication
Date de publication:
09 2019
09 2019
Historique:
received:
07
06
2019
revised:
11
07
2019
accepted:
11
07
2019
pubmed:
16
7
2019
medline:
6
5
2020
entrez:
16
7
2019
Statut:
ppublish
Résumé
The endogenous production of enzymes as zymogens provides a means to control catalytic activities. Here, we describe the heterologous production of ribonuclease 1 (RNase 1), which is the most prevalent secretory ribonuclease in humans, as a zymogen. In folded RNase 1, the N and C termini flank the enzymic active site. By using intein-mediated cis-splicing, we created circular proteins in which access to the active site of RNase 1 is obstructed by an amino-acid sequence that is recognized by the HIV-1 protease. Installing a sequence that does not perturb the RNase 1 fold led to only modest inactivation. In contrast, the ancillary truncation of residues from each terminus led to a substantial decrease in the catalytic activity of the zymogen with the maintenance of thermostability. For optimized zymogens, activation by HIV-1 protease led to a > 10
Identifiants
pubmed: 31306518
doi: 10.1002/pro.3686
pmc: PMC6699097
doi:
Substances chimiques
Enzyme Precursors
0
Ribonuclease, Pancreatic
EC 3.1.27.5
HIV Protease
EC 3.4.23.-
p16 protease, Human immunodeficiency virus 1
EC 3.4.23.-
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
1713-1719Subventions
Organisme : NIGMS NIH HHS
ID : T32 GM008349
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM044783
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA073808
Pays : United States
Informations de copyright
© 2019 The Protein Society.
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