Literature summary for 3.4.22.46 extracted from

Nogueira Santos, J.A.; Assis, D.M.; Gouvea, I.E.; Judice, W.A.; Izidoro, M.A.; Juliano, M.A.; Skern, T.; Juliano, L.
Foot and mouth disease leader protease (Lb(pro)): Investigation of prime side specificity allows the synthesis of a potent inhibitor (2011), Biochimie, 94, 711-718.

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Application

Application	Comment	Organism
drug development	the enzym eis a target for inhibitor design for inhibition of viral replication	Foot-and-mouth disease virus

Inhibitors

Inhibitors	Comment	Organism	Structure
CA074	epoxide-based inhibitor of cysteine proteinases, two-step overall irreversible inhibition, with step one being reversible and step two irreversible	Foot-and-mouth disease virus
E64	epoxide-based inhibitor of cysteine proteinases, two-step overall irreversible inhibition, with step one being reversible and step two irreversible. Extending E64 by addition of the dipeptide R-P to a compound termed E64-R-P-NH2, which irreversibly inhibits Lbpro with a Ki of 30 nM and k4 of 0.01/min, can serve as the basis for design of specific inhibitors of FMDV replication	Foot-and-mouth disease virus
E64-R-P-NH2	extending E64 by addition of the dipeptide R-P to a compound termed E64-R-P-NH2, which irreversibly inhibits Lbpro with a Ki of 30 nM and k4 of 0.01/min, can serve as the basis for design of specific inhibitors of FMDV replication	Foot-and-mouth disease virus

Natural Substrates/ Products (Substrates)

Natural Substrates	Organism	Comment (Nat. Sub.)	Natural Products	Comment (Nat. Pro.)	Rev.	Reac.
eukaryotic initiation factor 4G + H2O	Foot-and-mouth disease virus	Lbpro cleaves two homologues of the host cell protein. Lbpro possesses specific binding sites at the non-prime side from S1 down to S7	?	-	?
additional information	Foot-and-mouth disease virus	the leader protease, Lbpro, performs the initial cleavage by freeing itself from the growing polypeptide chain. Lbpro is not only one of the smallest papain-like cysteine peptidases but also one of the most specific. It has high prime side specificity at least down to the S' 5 site. It can still however cleave between both K-G and G-R pairs	?	-	?

Organism

Organism	UniProt	Comment	Textmining
Foot-and-mouth disease virus	-	FMDV	-

Substrates and Products (Substrate)

Substrates	Comment Substrates	Organism	Products	Comment (Products)	Rev.	Reac.
Abz-KLKGAGQ-EDDnp + H2O	hydrolysis of FRET peptides	Foot-and-mouth disease virus	Abz-KLK + GAGQ-EDDnp	-	?
eukaryotic initiation factor 4G + H2O	Lbpro cleaves two homologues of the host cell protein. Lbpro possesses specific binding sites at the non-prime side from S1 down to S7	Foot-and-mouth disease virus	?	-	?
additional information	the leader protease, Lbpro, performs the initial cleavage by freeing itself from the growing polypeptide chain. Lbpro is not only one of the smallest papain-like cysteine peptidases but also one of the most specific. It has high prime side specificity at least down to the S' 5 site. It can still however cleave between both K-G and G-R pairs	Foot-and-mouth disease virus	?	-	?

Synonyms

Synonyms	Comment	Organism
Lbpro	-	Foot-and-mouth disease virus
leader protease	-	Foot-and-mouth disease virus

Temperature Optimum [°C]

Temperature Optimum [°C]	Temperature Optimum Maximum [°C]	Comment	Organism
37	-	assay at	Foot-and-mouth disease virus

pH Optimum

pH Optimum Minimum	pH Optimum Maximum	Comment	Organism
7.8	-	assay at	Foot-and-mouth disease virus

Ki Value [mM]

Ki Value [mM]	Ki Value maximum [mM]	Inhibitor	Comment	Organism	Structure
additional information	-	additional information	kinetics mechanism of two-step overall irreversible inhibition by cysteinase inhibitors	Foot-and-mouth disease virus
0.00003	-	E64-R-P-NH2	pH 7.8, 37°C	Foot-and-mouth disease virus
0.0034	-	E64	pH 7.8, 37°C	Foot-and-mouth disease virus
0.0116	-	CA074	pH 7.8, 37°C	Foot-and-mouth disease virus

General Information

General Information	Comment	Organism
physiological function	foot and mouth disease virus expresses its genetic information as a single polyprotein that is translated from the single-stranded RNA genome. The leader protease, Lbpro, performs the initial cleavage by freeing itself from the growing polypeptide chain. Subsequently, Lbpro cleaves the two homologues of the host cell protein eukaryotic initiation factor 4G, eIF4G. Lbpro possesses specific binding sites at the non-prime side from S1 down to S7	Foot-and-mouth disease virus

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Release 2023.1 (January 2023)