Transcript What is MEROPS ?

What is MEROPS ?
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Database of Peptidases and their Inhibitors
More Specific than Pfam, containing in depth,
expert details about each entry
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Hierarchical classification
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Accessed at http://merops.sanger.ac.uk/
“SLEDGEHAMMER” PEPTIDASES
Peptidases that cleave many bonds in a protein, reducing it to peptides
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Physiological
food digestion (pepsin)
intracellular protein turnover (proteasome, cathepsin D)
tissue remodelling (collagenase 1, gelatinases A and B)
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Pathological
parasite invasion (cruzipain)
arthritis, emphysema, tumour invasion
Biotechnological
cheese making (chymosin)
biological washing powders (subtilisin)
meat tenderizer (papain)
protein sequencing (trypsin, chymotrypsin, pepsin)
“CHISEL” PEPTIDASES
Peptidases that cleave just one or two bonds in a protein
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Physiological
protein biosynthesis (methionyl aminopeptidase, signal peptidase)
apoptosis (caspases, granzyme B)
blood coagulation (factor Xa)
complement assembly (C1r, C1s)
activation of bioactive peptides and hormones (furin, kexin, renin)
destruction of bioactive peptides (neprilysin)
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Pathological
RNA viral polyprotein processing (retropepsin)
DNA virus protein processing (adenain, assemblin)
bacterial lethal factors (tetanus, anthrax)
Alzheimer’s disease
Biotechnological
Purification of expressed proteins (enteropeptidase, TEV
proteinase)
The MEROPS hierarchy
Clan
Family
C
1
1
C
1
3
C
D
C
1
4
Peptidase
Species
37
C
2
5
C
5
0
180
1942
C14.001
human (MER00850)
mouse (MER00851)
rat
(MER00852)
pig
(MER12113)
horse (MER06237)
gerbil (MER20111)
24896
THE PEPTIDASE UNIT
I
II
III
Calpain I
C
H
C
H
C
H
C
H
Calpain 7
Calpain 10
SOL
Peptidase unit (domain II)
zinc finger
domain III
PBH domain
calcium-binding (domain IV)
MIT domain
IV
TYPE PEPTIDASES
caspase 1 (rat)
DIRECT
E < 0.001
caspase 1 (human)
caspase 2 (human)
caspase 9 (human)
caspase 3 (dog)
E > 0.001
TRANSITIVE
E < 0.001
DIRECT
caspase 3 (human)
DATA SOURCES
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FastA searches of UniProt
FastA searches of proteomes from completely
sequenced genomes
TBlastN searches of EMBL
FastPan searches of human and mouse ESTs
Sequences in papers
The MEROPS hierarchy
Clan
Family
C
1
1
C
1
3
C
D
C
1
4
Peptidase
Species
37
C
2
5
C
5
0
180
1942
C14.001
human (MER00850)
mouse (MER00851)
rat
(MER00852)
pig
(MER12113)
horse (MER06237)
gerbil (MER20111)
24896
ADDING FAMILIES TO CLANS
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Every clan has a type peptidase
A peptidase family is added to a clan if
– a peptidase has a similar tertiary structure to the
clan type example, as defined by
● the crystallographers
● DALI (z score > 5.99)
● SCOP
– the active site residues are in the same order in
the sequence as that of the clan type example
The MEROPS hierarchy
Clan
Family
C
1
1
C
1
3
C
D
C
1
4
Peptidase
Species
37
C
2
5
C
5
0
180
1942
C14.001
human (MER00850)
mouse (MER00851)
rat
(MER00852)
pig
(MER12113)
horse (MER06237)
gerbil (MER20111)
24896
WHAT IS A PEPTIDASE?
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Similar substrate specificity (known or predicted)
Sequence homology from amino to carboxy terminus
Derived from the same node on a cladogram
Inhibitors
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MEROPS also contains information about peptidase
inhibitors
There is a hierarchical classification of inhibitors.
The design and look of the inhibitor pages is very similar
to the peptidase.
SUMMARY
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Peptidases are enzymes that are difficult to classify by
substrate specificity. The MEROPS database provides an
alternative, hierarchical classification by domain structure
(CLAN), sequence (FAMILY) and specificity (PEPTIDASE).
There are no families of hypothetical proteins in MEROPS.
A family contains peptidases of only one catalytic type.
A clan, however, can consist of families of peptidases of
different catalytic types.
Homologues can be predicted to be peptidases
Further Reading
Rawlings ND, Tolle DP, Barrett AJ. MEROPS: the peptidase database.
Nucleic Acids Res. 2004 Jan 1;32 Database issue:D160-4. PMID:
14681384
Rawlings ND, Tolle DP, Barrett AJ. Evolutionary families of peptidase
inhibitors. Biochem J. 2004 Mar 15; (Pt 3):705-16. Review. PMID:
14705960
Handbook of Proteolyic Enzymes. Neil D. Rawlings et al. Academic
Press
Or mail: [email protected]
Practical
Now go to the following page:
http://www.sanger.ac.uk/Users/rdf/EMBO/section4.html