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PR00931

Identifier
MICOLLPTASE  [View Relations]  [View Alignment]  
Accession
PR00931
No. of Motifs
5
Creation Date
09-SEP-1998  (UPDATE 07-JUN-1999)
Title
Microbial collagenase metalloprotease (M9) signature
Database References

PROSITE; PS00142 ZINC_PROTEASE
BLOCKS; BL00142
PFAM; PF00099 zn-protease
INTERPRO; IPR002169
Literature References
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 M9 - Clan MA - Microbial collagenase
http://www.bi.bbsrc.ac.uk/merops/famcards/m9.htm
 
4. BARRETT, A.J., RAWLINGS, N.D. AND WOESSNER, J.F.
Vibrio collagenase.
IN HANDBOOK OF PROTEOLYTIC ENZYMES, ACADEMIC PRESS, 1998, CHAPTER 367, 
PP.1096-1098.
 
5. BARRETT, A.J., RAWLINGS, N.D. AND WOESSNER, J.F.
Clostridium collagenases.
IN HANDBOOK OF PROTEOLYTIC ENZYMES, ACADEMIC PRESS, 1998, CHAPTER 368, 
PP.1098-1102.
 
6. MATSUSHITA, O., YOSHIHARA, K., KATAYAMA, S., MINAMI, J. AND OKABE, A.
Purification and characterization of Clostridium perfringens 120-kilodalton
collagenase and nucleotide sequence of the corresponding gene.
J.BACTERIOL. 176 149-156 (1994). 

Documentation
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].
 
Microbial collagenases have been identified from bacteria of both the 
Vibrio and Clostridium genuses. They are zinc-containing metallopeptidases
that belong to the M25 protease family, which form part of the MA clan 
[1,3]. Collagenase is used during bacterial attack to degrade the collagen
barrier of the host during invasion. Vibrio bacteria are non-pathogenic, and 
are sometimes used in hospitals to remove dead tissue from burns and ulcers
[4]. Clostrium histolyticum is a pathogen that causes gas gangrene; 
nevertheless, the isolated collagenase has been used to treat bed sores [5].
Collagen cleavage occurs at an Xaa+Gly in Vibrio bacteria and at Yaa+Gly
bonds in Clostridium collagenases [4,5].
 
Analysis of the primary structure of the gene product from Clostridium 
perfringens has revealed that the enzyme is produced with a stretch of 86 
residues that contain a putative signal sequence [6]. Within this stretch
is found PLGP, an amino acid sequence typical of collagenase substrates.
This sequence may thus be implicated in self-processing of the 
collagenase [6].
 
MICOLLPTASE is a 5-element fingerprint that provides a signature for 
microbial collagenase zinc metallopeptidases (M9). The fingerprint was
derived from an initial alignment of 4 sequences: the motifs were drawn from
conserved regions spanning virtually the full alignment length - motif 4
includes the region encoded by the PROSITE pattern ZINC_PROTEASE (PS00142),
which describes the HEXXH active site; and motif 5 contains the active site
glutamate. Two iterations on OWL31.1 were required to reach convergence,
at which point a true set comprising 8 sequences was identified. 
 
An update on SPTR37_9f identified a true set of 5 sequences, and 1
partial match.
Summary Information
   5 codes involving  5 elements
1 codes involving 4 elements
0 codes involving 3 elements
0 codes involving 2 elements
Composite Feature Index
555555
401111
300000
200000
12345
True Positives
COLA_CLOPE    COLA_VIBAL    COLA_VIBPA    O54108        
Q46085
True Positive Partials
Codes involving 4 elements
O86030
Sequence Titles
COLA_CLOPE  MICROBIAL COLLAGENASE PRECURSOR (EC 3.4.24.3) (120 KD COLLAGENASE) - CLOSTRIDIUM PERFRINGENS. 
COLA_VIBAL MICROBIAL COLLAGENASE PRECURSOR (EC 3.4.24.3) - VIBRIO ALGINOLYTICUS.
COLA_VIBPA MICROBIAL COLLAGENASE PRECURSOR (EC 3.4.24.3) - VIBRIO PARAHAEMOLYTICUS.
O54108 PUTATIVE SECRETED PROTEASE - STREPTOMYCES COELICOLOR.
Q46085 COLLAGENASE PRECURSOR - CLOSTRIDIUM HISTOLYTICUM.

O86030 COLLAGENASE - VIBRIO CHOLERAE.
Scan History
OWL30_2    1  50   NSINGLE    
OWL31_1 1 50 NSINGLE
SPTR37_9f 2 100 NSINGLE
Initial Motifs
Motif 1  width=19
Element Seqn Id St Int Rpt
ELETLFLYLRAGYYAEFYN COLA_VIBAL 144 144 -
GIPTLVEFLRAGYYLGFYN COLA_CLOPE 159 159 -
RLENYGEFIRAAYYVRYNA AF080248 97 97 -
VLENLGEFVRAAYYVRYNA COLA_VIBPA 97 97 -

Motif 2 width=15
Element Seqn Id St Int Rpt
VEVAVFASNDSYVDY COLA_VIBPA 374 258 -
VEVVVFANNSSYVNY AF080248 374 258 -
LTVVIYNSPEEYKLN COLA_CLOPE 447 269 -
LQVNIFDSSTDYGKY COLA_VIBAL 415 252 -

Motif 3 width=17
Element Seqn Id St Int Rpt
IFDISTDNGGMYLEGDP COLA_VIBAL 433 3 -
LFGNTTDNGGQYLEGTP COLA_VIBPA 392 3 -
LFGNTTDNGGQYLEGNP AF080248 391 2 -
INGFSTDNGGIYIENIG COLA_CLOPE 464 2 -

Motif 4 width=19
Element Seqn Id St Int Rpt
EHEYTHYLDARFNQYGSFS AF080248 433 25 -
RHEFTHYLQGRYVVPGMWG COLA_CLOPE 501 20 -
EHEYVHYLDGRFDLYGGFS COLA_VIBAL 476 26 -
EHEYTHYLDARFNQYGSFS COLA_VIBPA 434 25 -

Motif 5 width=16
Element Seqn Id St Int Rpt
EKIVWWSEGIAEYVAQ COLA_VIBAL 498 3 -
GHIVWWLEGFAEYMHY COLA_VIBPA 458 5 -
GVLTWYEEGTAEFFAG COLA_CLOPE 527 7 -
GHIVWWLEGFAEYMHY AF080248 457 5 -
Final Motifs
Motif 1  width=19
Element Seqn Id St Int Rpt
GIPTLVEFLRAGYYLGFYN COLA_CLOPE 159 159 -
GMPQLVLYLRAGYYVHYYN O54108 189 189 -
ELETLFLYLRAGYYAEFYN COLA_VIBAL 144 144 -
GIPTLVEVVRAGFYLGFHN Q46085 114 114 -
VLENLGEFVRAAYYVRYNA COLA_VIBPA 97 97 -

Motif 2 width=15
Element Seqn Id St Int Rpt
LTVVIYNSPEEYKLN COLA_CLOPE 447 269 -
IEVVVFDSSTDYQTY O54108 463 255 -
LQVNIFDSSTDYGKY COLA_VIBAL 415 252 -
LTMVIYNSPEEYKLN Q46085 400 267 -
VEVAVFASNDSYVDY COLA_VIBPA 374 258 -

Motif 3 width=17
Element Seqn Id St Int Rpt
INGFSTDNGGIYIENIG COLA_CLOPE 464 2 -
MYGIDTNNGGMYLEGNP O54108 481 3 -
IFDISTDNGGMYLEGDP COLA_VIBAL 433 3 -
LYGYDTNNGGMYIEPEG Q46085 417 2 -
LFGNTTDNGGQYLEGTP COLA_VIBPA 392 3 -

Motif 4 width=19
Element Seqn Id St Int Rpt
RHEFTHYLQGRYVVPGMWG COLA_CLOPE 501 20 -
NHEYTHYLDGRFDMYGDFN O54108 524 26 -
EHEYVHYLDGRFDLYGGFS COLA_VIBAL 476 26 -
RHEYTHYLQGRYAVPGQWG Q46085 454 20 -
EHEYTHYLDARFNQYGSFS COLA_VIBPA 434 25 -

Motif 5 width=16
Element Seqn Id St Int Rpt
GVLTWYEEGTAEFFAG COLA_CLOPE 527 7 -
TPTIWWVEGFAEYVSY O54108 547 4 -
EKIVWWSEGIAEYVAQ COLA_VIBAL 498 3 -
DRLTWYEEGGAELFAG Q46085 480 7 -
GHIVWWLEGFAEYMHY COLA_VIBPA 458 5 -