WORKLIST ENTRIES (1):

MICOLLPTASE View alignment      Microbial collagenase metalloprotease (M9) signature
 Type of fingerprint: COMPOUND with 5  elements
Links:
   PRINTS; PR00756 ALADIPTASE; PR00791 PEPDIPTASEA; PR00730 THERMOLYSIN
   PRINTS; PR00787 NEUTRALPTASE; PR00782 LSHMANOLYSIN; PR00997 FRAGILYSIN
   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; IPR002169
   PROSITE; PS00142 ZINC_PROTEASE
   PFAM; PF00099 

 Creation date 09-SEP-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 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, PP.1096-1098.

   5. BARRETT, A.J., RAWLINGS, N.D. AND WOESSNER, J.F.
   Clostridium collagenases.
   IN HANDBOOK OF PROTEOLYTIC ENZYMES, ACADEMIC PRESS, 1998, 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). 

   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 FINGERPRINT INDEX
  
    5|   5    5    5    5    5  
    4|   0    1    1    1    1  
    3|   0    0    0    0    0  
    2|   0    0    0    0    0  
   --+--------------------------
     |   1    2    3    4    5  

True positives..
 COLA_CLOPE     O54108         COLA_VIBAL     Q46085         
 COLA_VIBPA     
Subfamily:  Codes involving 4 elements
 Subfamily True positives..
 O86030         


  PROTEIN TITLES
   COLA_CLOPE       MICROBIAL COLLAGENASE PRECURSOR (EC 3.4.24.3) (120 KD COLLAG
   O54108           PUTATIVE SECRETED PROTEASE - STREPTOMYCES COELICOLOR.
   COLA_VIBAL       MICROBIAL COLLAGENASE PRECURSOR (EC 3.4.24.3) - VIBRIO ALGIN
   Q46085           COLLAGENASE PRECURSOR - CLOSTRIDIUM HISTOLYTICUM.
   COLA_VIBPA       MICROBIAL COLLAGENASE PRECURSOR (EC 3.4.24.3) - VIBRIO PARAH
 
   O86030           COLLAGENASE - VIBRIO CHOLERAE.

SCAN HISTORY OWL30_2 1 50 NSINGLE OWL31_1 1 50 NSINGLE SPTR37_9f 2 100 NSINGLE INITIAL MOTIF SETS MICOLLPTASE1 Length of motif = 19 Motif number = 1 Microbial collagenase motif I - 1 PCODE ST INT GIPTLVEFLRAGYYLGFYN COLA_CLOPE 159 159 ELETLFLYLRAGYYAEFYN COLA_VIBAL 144 144 VLENLGEFVRAAYYVRYNA COLA_VIBPA 97 97 RLENYGEFIRAAYYVRYNA AF080248 97 97 MICOLLPTASE2 Length of motif = 15 Motif number = 2 Microbial collagenase motif II - 1 PCODE ST INT LTVVIYNSPEEYKLN COLA_CLOPE 447 269 LQVNIFDSSTDYGKY COLA_VIBAL 415 252 VEVAVFASNDSYVDY COLA_VIBPA 374 258 VEVVVFANNSSYVNY AF080248 374 258 MICOLLPTASE3 Length of motif = 17 Motif number = 3 Microbial collagenase motif III - 1 PCODE ST INT INGFSTDNGGIYIENIG COLA_CLOPE 464 2 IFDISTDNGGMYLEGDP COLA_VIBAL 433 3 LFGNTTDNGGQYLEGTP COLA_VIBPA 392 3 LFGNTTDNGGQYLEGNP AF080248 391 2 MICOLLPTASE4 Length of motif = 19 Motif number = 4 Microbial collagenase motif IV - 1 PCODE ST INT RHEFTHYLQGRYVVPGMWG COLA_CLOPE 501 20 EHEYVHYLDGRFDLYGGFS COLA_VIBAL 476 26 EHEYTHYLDARFNQYGSFS COLA_VIBPA 434 25 EHEYTHYLDARFNQYGSFS AF080248 433 25 MICOLLPTASE5 Length of motif = 16 Motif number = 5 Microbial collagenase motif V - 1 PCODE ST INT GVLTWYEEGTAEFFAG COLA_CLOPE 527 7 EKIVWWSEGIAEYVAQ COLA_VIBAL 498 3 GHIVWWLEGFAEYMHY COLA_VIBPA 458 5 GHIVWWLEGFAEYMHY AF080248 457 5 FINAL MOTIF SETS MICOLLPTASE1 Length of motif = 19 Motif number = 1 Microbial collagenase motif I - 2 PCODE ST INT GIPTLVEFLRAGYYLGFYN COLA_CLOPE 159 159 GMPQLVLYLRAGYYVHYYN O54108 189 189 ELETLFLYLRAGYYAEFYN COLA_VIBAL 144 144 GIPTLVEVVRAGFYLGFHN Q46085 114 114 VLENLGEFVRAAYYVRYNA COLA_VIBPA 97 97 MICOLLPTASE2 Length of motif = 15 Motif number = 2 Microbial collagenase motif II - 2 PCODE ST INT LTVVIYNSPEEYKLN COLA_CLOPE 447 269 IEVVVFDSSTDYQTY O54108 463 255 LQVNIFDSSTDYGKY COLA_VIBAL 415 252 LTMVIYNSPEEYKLN Q46085 400 267 VEVAVFASNDSYVDY COLA_VIBPA 374 258 MICOLLPTASE3 Length of motif = 17 Motif number = 3 Microbial collagenase motif III - 2 PCODE ST INT INGFSTDNGGIYIENIG COLA_CLOPE 464 2 MYGIDTNNGGMYLEGNP O54108 481 3 IFDISTDNGGMYLEGDP COLA_VIBAL 433 3 LYGYDTNNGGMYIEPEG Q46085 417 2 LFGNTTDNGGQYLEGTP COLA_VIBPA 392 3 MICOLLPTASE4 Length of motif = 19 Motif number = 4 Microbial collagenase motif IV - 2 PCODE ST INT RHEFTHYLQGRYVVPGMWG COLA_CLOPE 501 20 NHEYTHYLDGRFDMYGDFN O54108 524 26 EHEYVHYLDGRFDLYGGFS COLA_VIBAL 476 26 RHEYTHYLQGRYAVPGQWG Q46085 454 20 EHEYTHYLDARFNQYGSFS COLA_VIBPA 434 25 MICOLLPTASE5 Length of motif = 16 Motif number = 5 Microbial collagenase motif V - 2 PCODE ST INT GVLTWYEEGTAEFFAG COLA_CLOPE 527 7 TPTIWWVEGFAEYVSY O54108 547 4 EKIVWWSEGIAEYVAQ COLA_VIBAL 498 3 DRLTWYEEGGAELFAG Q46085 480 7 GHIVWWLEGFAEYMHY COLA_VIBPA 458 5

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