Family I50

Family

Summary Holotypes Alignment Tree Genomes Structure Literature Architecture

I50A

Summary Holotypes Alignment Tree Genomes Literature

I50B

Summary Holotypes Alignment Genomes Literature

Summary for family I50

Name	Inhibitor family I50 (p35 family)
Family type peptidase	I50.001 - baculovirus P35 caspase inhibitor (Spodoptera litura nucleopolyhedrovirus), MEROPS Accession MER0018610 (inhibitor unit: 1-296)
Content of family	Inhibitor family I50 contains inhibitors of capsases, peptidases in family C14.
History	Identifier created: MEROPS 6.1 (10 January 2003) Clem et al. (1991) identified the product of the baculovirus P35 gene (I50.001) as responsible for blocking the apoptotic response of virus-infected insect cells.
Peptidases inhibited	Zhou et al. (1998) reported that purified recombinant P35 inhibits human caspase-1, -3, -6, -7, -8, and -10 with k_ass values from 1.2 x 10(3) to 7 x 10(5) (M-1 s-1), and with upper limits of Ki values from 0.1 to 9 nM, whereas inhibition of twelve unrelated serine or cysteine peptidases was insignificant. Later, potent inhibition of gingipain R (C25.001) (also in clan CD) was reported by Snipas et al. (2001). The insect caspase DRONC (C14.019) is not inhibited by P35, but is inhibited by the second member of the family, P49 (I50.002) (Jabbour et al., 2002).
Mechanism of inhibition	The mechanism is a 'trapping' one that depends upon a conformational change in the inhibitor that is triggered by cleavage of the reactive site bond. As such it can be compared with those of the serpins (family I4) and macroglobulins (I39). In P35, cleavage of the reactive site peptide bond proceeds as far as the formation of a thioester intermediate, but at this stage the catalytic mechanism is disabled, so that hydrolysis of the thioester does not occur. The inhibitor adopts a new, stable conformation in which its N-terminus is inserted into the active site cleft of the enzyme (Fisher et al., 1999; Xu et al., 2001; Riedl et al., 2001).
Molecular structure	A number of crystal structures are available for P35 (see the Structure page).
Clan	IQ

Distribution of family	Bacteria	-
	Archaea	details
	Protozoa	-
	Fungi	-
	Plants	-
	Animals	details
	Viruses	details

Biological functions	The inhibitors of family I50 (together with those in family I32) facilitate the replication of baculoviruses in their insect hosts by blocking the apoptosis of the cells that would normally follow viral infection (Del Pozo & Lam, 2003).
Pharmaceutical and biotech relevance	The finding that gene transfer of P35 by an adenoviral vector protects human cerebral neurons from apoptosis has led to the proposal that P35 transduction of neurons could be therapeutically useful in the treatment of human neurodegenerative diseases (Miagkov et al., 2004).
Reviews	Zhou & Salvesen (2000)
Statistics for family I50	Sequences:	35
	Identifiers:	3
	Identifiers with PDB entries:	1
Downloadable files	Sequence library (FastA format)
	Sequence alignment (FastA format)
	Phylogenetic tree (Newick format)

Subfamily I50A
Name	Inhibitor subfamily I50A
Subfamily type peptidase	I50.001 - baculovirus P35 caspase inhibitor (Spodoptera litura nucleopolyhedrovirus), MEROPS Accession MER0018610 (inhibitor unit: 1-296)
Other databases	INTERPRO	IPR003429
	PFAM	PF02331
	SCOP	49895
Downloadable files	Sequence library [FastA format]
	Sequence alignment [FastA format]
	Phylogenetic tree [Newick format]

Inhibitors and Homologues	MEROPS ID	Structure
baculovirus P35 caspase inhibitor	I50.001	Yes
baculovirus P49 caspase inhibitor	I50.002	-
Subfamily I50A unassigned peptidases	unassigned	-

Subfamily I50B
Name	Inhibitor subfamily I50B
Subfamily type peptidase	I50.003 - p35 homologue (Amsacta moorei entomopoxvirus) (Amsacta moorei entomopoxvirus), MEROPS Accession MER0079656 (inhibitor unit: 7-261)
Other databases	INTERPRO	IPR003429
	PFAM	PF02331
Downloadable files	Sequence library [FastA format]
	Sequence alignment [FastA format]
	Phylogenetic tree [Newick format]

Inhibitors and Homologues	MEROPS ID	Structure
p35 homologue (Amsacta moorei entomopoxvirus)	I50.003	-
Subfamily I50B unassigned peptidases	unassigned	-