WORKLIST ENTRIES (1):
FRAGILYSIN View alignment Fragilysin metallopeptidase (M10C) enterotoxin signature
Type of fingerprint: COMPOUND with 7 elements
Links:
PRINTS; PR00756 ALADIPTASE; PR00791 PEPDIPTASEA; PR00730 THERMOLYSIN
PRINTS; PR00787 NEUTRALPTASE; PR00782 LSHMANOLYSIN; PR00931 MICOLLPTASE
PRINTS; PR00786 NEPRILYSIN; PR00765 CRBOXYPTASEA; PR00932 AMINO1PTASE
PRINTS; PR00789 OSIALOPTASE; PR00933 BLYTICPTASE; PR00934 XHISDIPTASE
PRINTS; PR00919 THERMOPTASE; PR00998 CRBOXYPTASET; PR00768 DEUTEROLYSIN
PRINTS; PR00999 FUNGALYSIN; PR01000 SREBPS2PTASE
INTERPRO; IPR001843
PROSITE; PS00142 ZINC_PROTEASE
PFAM; PF00099
Creation date 21-DEC-1998; UPDATE 07-JUN-1999
1. RAWLINGS, N.D. AND BARRETT, A.J.
Evolutionary families of metallopeptidases.
METHODS ENZYMOL. 248 183-228 (1995).
2. RAWLINGS, N.D. AND BARRETT, A.J.
MEROPS - Peptidase Database
http://www.bi.bbsrc.ac.uk/merops/merops.htm
3. RAWLINGS, N.D. AND BARRETT, A.J.
Family M10C - Clan MB - Fragilysin
http://www.bi.bbsrc.ac.uk/merops/famcards/m10.htm
4. BARRETT, A.J., RAWLINGS, N.D. AND WOESSNER, J.F.
Fragilysin.
IN HANDBOOK OF PROTEOLYTIC ENZYMES, ACADEMIC PRESS, 1998, PP.1211-1213.
Metalloproteases are the most diverse of the four main types of protease,
with more than 30 families identified to date [1]. Of these, around
half contain the HEXXH motif, which has been shown in crystallographic
studies to form part of the metal-binding site [1]. The HEXXH motif is
relatively common, but can be more stringently defined for metallo-
proteases as abXHEbbHbc, where a is most often valine or threonine and
forms part of the S1' subsite in thermolysin and neprilysin, b is an
uncharged residue, and c a hydrophobic residue. Proline is never found
in this site, possibly because it would break the helical structure
adopted by this motif in metalloproteases [1].
Metalloproteases can be split into five groups on the basis of their metal-
binding residues: the first three contain the HEXXH motif, the other two
do not [1]. In the first group, a glutamic acid completes the active site -
these are termed HEXXH+E: all families in this group show some sequence
relationship and have been assigned to clan MA [1]. The second group, which
have a third histidine as the extra metal-binding residue, are termed
HEXXH+H and are grouped into clan MB on the basis of their inter-relation-
ship[1]. In the third group, the additional metal-binding residues are
unidentified. The fourth group is diverse - the metal-binding residues are
known but do not form the HEXXH motif. And the fifth group comprises the
remaining families where the metal-binding residues are as yet unknown [1,2].
Fragilysin is a zinc-containing enterotoxin that belongs to the M10C
metallopeptidase family, which form part of the MB clan [3]. It is produced
by around 10% of pathogenic strains of the bacterium Bacteroides fragilis
(which is found in mammalian large intestines in approximately the same
quantities as Esherichia coli), and has been shown to cause diarrhoea.
The fragilysin enterotoxin acts by proteolytically damaging the intestinal
epithelium (at the tight junctions and basement membranes), causing the
release of fluids into the intestinal lumen. In view of the intrinsic
resistance of the intestinal tract to protease activity (it being constantly
bathed in digestive proteases), an enzyme activity capable of puncturing
the epithelium is considered rather unusual. However the exact mechanism of
action of the protein is unknown [4].
FRAGILYSIN is a 7-element fingerprint that provides a signature for
fragilysin. The fingerprint was derived from an initial alignment of 2
sequences: the motifs were drawn from conserved regions spanning virtually
the full alignment length - motifs 6 and 7 span the region encoded by
PROSITE pattern ZINC_PROTEASE (PS00142), which describes the HEXXH active
site; and motif 7 contains three potentially completely conserved residues
that could be candidates for the additional active site histidine or
glutamic acid. Two iterations on OWL31.1 were required to reach convergence,
at which point a true set comprising 5 sequences was identified. A single
partial match was also found, S75941B, a fragilysin C-terminal fragment.
An update on SPTR37_9f identified a true set of 4 sequences.
SUMMARY INFORMATION
4 codes involving 7 elements
0 codes involving 6 elements
0 codes involving 5 elements
0 codes involving 4 elements
0 codes involving 3 elements
0 codes involving 2 elements
COMPOSITE FINGERPRINT INDEX
7| 4 4 4 4 4 4 4
6| 0 0 0 0 0 0 0
5| 0 0 0 0 0 0 0
4| 0 0 0 0 0 0 0
3| 0 0 0 0 0 0 0
2| 0 0 0 0 0 0 0
--+------------------------------------
| 1 2 3 4 5 6 7
True positives..
O68424 ENTM_BACFR O68892 O05091
PROTEIN TITLES
O68424 PUTATIVE METALLOPROTEASE II - BACTEROIDES FRAGILIS.
ENTM_BACFR FRAGILYSIN PRECURSOR (EC 3.4.24.74) (ENTEROTOXIN) - BACTEROI
O68892 METALLOPROTEASE TOXIN-3 - BACTEROIDES FRAGILIS.
O05091 METALLOPROTEASE TOXIN-2 - BACTEROIDES FRAGILIS.
SCAN HISTORY
OWL31_1 2 50 NSINGLE
SPTR37_9f 2 5 NSINGLE
INITIAL MOTIF SETS
FRAGILYSIN1 Length of motif = 16 Motif number = 1
Fragilysin enterotoxin metalloprotease motif I - 1
PCODE ST INT
VRLFNGRDKDSTSFIL ENTM_BACFR 98 98
VYLFEGQDKDSINAIL AF056297 90 90
FRAGILYSIN2 Length of motif = 17 Motif number = 2
Fragilysin enterotoxin metalloprotease motif II - 1
PCODE ST INT
YIAYKEAQMMNEIAEFY ENTM_BACFR 131 17
YIVYKDKERMAEIANYY AF056297 123 17
FRAGILYSIN3 Length of motif = 18 Motif number = 3
Fragilysin enterotoxin metalloprotease motif III - 1
PCODE ST INT
TRSAGKDIVSVKINIDKA ENTM_BACFR 171 23
TRSGNSDIKNIRVDITKA AF056297 163 23
FRAGILYSIN4 Length of motif = 17 Motif number = 4
Fragilysin enterotoxin metalloprotease motif IV - 1
PCODE ST INT
GLEGFTASLKSNPKAEG ENTM_BACFR 287 98
ALESFQNYLRSWDEVKG AF056297 279 98
FRAGILYSIN5 Length of motif = 16 Motif number = 5
Fragilysin enterotoxin metalloprotease motif V - 1
PCODE ST INT
DDQIYFLIRWGTWDNK ENTM_BACFR 305 1
DKKPYILLRDGTWDSG AF056297 297 1
FRAGILYSIN6 Length of motif = 20 Motif number = 6
Fragilysin enterotoxin metalloprotease motif VI - 1
PCODE ST INT
FEASGMSTTQLMYPGVMAHE ENTM_BACFR 338 17
FEVAAISTTSSSHPYTLAHE AF056297 333 20
FRAGILYSIN7 Length of motif = 17 Motif number = 7
Fragilysin enterotoxin metalloprotease motif VII - 1
PCODE ST INT
GHILGAEHTDNSKDLMY ENTM_BACFR 359 1
GHLLGAEHVDNEQDLMY AF056297 354 1
FINAL MOTIF SETS
FRAGILYSIN1 Length of motif = 16 Motif number = 1
Fragilysin enterotoxin metalloprotease motif I - 2
PCODE ST INT
VYLFEGQDKDSINAIL O68424 90 90
VRLFNGRDKDSTSFIL ENTM_BACFR 98 98
VYLFEGQDKDSINAIL O68892 90 90
VRLFNGRDKDSTSFIL O05091 90 90
FRAGILYSIN2 Length of motif = 17 Motif number = 2
Fragilysin enterotoxin metalloprotease motif II - 2
PCODE ST INT
YIVYKDKERMAEIANYY O68424 123 17
YIAYKEAQMMNEIAEFY ENTM_BACFR 131 17
YIVYKDKERMAEIANYY O68892 123 17
YIAYKEAQMMNEIAEFY O05091 123 17
FRAGILYSIN3 Length of motif = 18 Motif number = 3
Fragilysin enterotoxin metalloprotease motif III - 2
PCODE ST INT
TRSGKSDIKNIRIDITKA O68424 163 23
TRSAGKDIVSVKINIDKA ENTM_BACFR 171 23
TRSGNSDIKNIRVDITKA O68892 163 23
TRSAGKDLVSVKINIDKA O05091 163 23
FRAGILYSIN4 Length of motif = 17 Motif number = 4
Fragilysin enterotoxin metalloprotease motif IV - 2
PCODE ST INT
ALESFQNYLRSWDEVKG O68424 279 98
GLEGFTASLKSNPKAEG ENTM_BACFR 287 98
ALESFQNYLRSWDEVKG O68892 279 98
GLDGFTASLKANPKAEG O05091 279 98
FRAGILYSIN5 Length of motif = 16 Motif number = 5
Fragilysin enterotoxin metalloprotease motif V - 2
PCODE ST INT
DKKPYILLRDGTWDSG O68424 297 1
DDQIYFLIRWGTWDNK ENTM_BACFR 305 1
DKKPYILLRDGTWDSG O68892 297 1
DDQIYFLIRWGTWDNN O05091 297 1
FRAGILYSIN6 Length of motif = 20 Motif number = 6
Fragilysin enterotoxin metalloprotease motif VI - 2
PCODE ST INT
FEVAAISTTSSSHPYTLAHE O68424 333 20
FEASGMSTTQLMYPGVMAHE ENTM_BACFR 338 17
FEVAAISTTSSSHPYTLAHE O68892 333 20
FKASGMSTTQLMYPGVMAHE O05091 330 17
FRAGILYSIN7 Length of motif = 17 Motif number = 7
Fragilysin enterotoxin metalloprotease motif VII - 2
PCODE ST INT
GHLLGAEHVDNEQDLMY O68424 354 1
GHILGAEHTDNSKDLMY ENTM_BACFR 359 1
GHLLGAEHVDNEQDLMY O68892 354 1
GHILGARHADDPKDLMY O05091 351 1
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