WORKLIST ENTRIES (1):
THERMOLYSIN View alignment View Structure Thermolysin metalloprotease (M4) family signature
Type of fingerprint: COMPOUND with 4 elements
Links:
PRINTS; PR00756 ALADIPTASE; PR00791 PEPDIPTASEA; PR00787 NEUTRALPTASE
PRINTS; PR00782 LSHMANOLYSIN; PR00931 MICOLLPTASE; 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; IPR001570
PROSITE; PS00142 ZINC_PROTEASE
PDB; 1TMN 3Dinfo
SCOP; 1TMN
CATH; 1TMN
Creation date 10-FEB-1997; UPDATE 10-JUN-1999
1. RAWLINGS, N.D. AND BARRETT, A.J.
Evolutionary families of metallopeptidases.
METHODS ENZYMOL. 248 183-228 (1995).
Metalloproteases are the most diverse of the four main types of protease,
with more than 30 families identified to date [1]. Of these, approximately
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
quite common in proteins, 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 is a hydrophobic residue. Proline is never found
in this site, possibly because it would break the helical structure the
motif has been shown to form in metalloproteases [1].
Metalloproteases can be split into five groups on the basis of the metal-
binding residues: the first three contain the HEXXH motif, the other two
do not [1]. The first group contain an additional glutamic acid, which
completes the active site and are termed HEXXH+E: all families in this
group show some sequence similarity and have thus been grouped into clan
MA [1]. In the second group, a third histidine constitutes the extra metal-
binding residue: these are termed HEXXH+H and are grouped into clan MB [1].
The additional metal-binding residues in the third group are unidentified.
In the fourth group, the metal-binding residues are known, but in the fifth
group these residues are as yet unknown [1].
The thermolysin family (M4), part of the MA clan (HEXXH+E), is composed
only of secreted eubacterial endopeptidases [1]. The zinc-binding residues
are H-142, H-146 and E-166, with E-143 acting as the catalytic residue [1].
Thermolysin also contains 4 calcium-binding sites, which contribute to its
unusual thermostability [1]. The family also includes enzymes from a number
of pathogens, including Legionella and Listeria, and the protein pseudolysin,
all with a substrate specificity for an aromatic residue in the P1' position
[1]. Three-dimensional structure analysis has shown that the enzymes undergo
a hinge-bend motion during catalysis [1]. Pseudolysin has a broader
specificity, acting on large molecules such as elastin and collagen,
possibly due to its wider active site cleft [1].
THERMOLYSIN is a 4-element fingerprint that provides a signature for the
thermolysin metalloprotease (M4) family. The fingerprint was derived from
an initial alignment of 5 sequences: the motifs were drawn from conserved
regions surrounding the active site - motif 2 includes the region encoded
by PROSITE pattern ZINC_PROTEASE (PS00142), which contains the HEXXH motif,
the His residues of which provide the zinc ligands, the Glu being the
active site residue; and motif 3 contains the additional metal-binding
residue (E-166). Three iterations on OWL29.1 were required to reach
convergence, at which point a true set comprising 34 sequences was
identified. Two partial matches were also found: A38166 is a probable
elastase precursor that lacks a match with motif 4; and SMP_SERMA is an
extracellular minor metalloprotease precursor, a member of the M4 family,
that lacks a match with motif 1.
An update on SPTR37_9f identified a true set of 34 sequences, and 1
partial match.
SUMMARY INFORMATION
34 codes involving 4 elements
1 codes involving 3 elements
0 codes involving 2 elements
COMPOSITE FINGERPRINT INDEX
4| 34 34 34 34
3| 0 1 1 1
2| 0 0 0 0
--+---------------------
| 1 2 3 4
True positives..
NPRE_BACCL THER_BACST Q59223 Q59193
Q43880 Q48857 NPRE_BACBR NPRE_BACCE
O32309 NPRS_BACST Q45779 NPRM_BACME
NPRE_PAEPO THER_BACTH NPRE_BACAM NPRE_BACSU
Q44677 PRT1_ERWCA Q46237 NPRB_BACSU
SEPA_STAEP AURE_STAAU NPRV_VIBPR PRO1_LISMO
PRO2_LISMO EMPA_VIBAN O06694 P96176
HAPT_VIBCH ELAS_PSEAE PRZN_RENSA PROA_LEGPN
Q47786 PROA_LEGLO
Subfamily: Codes involving 3 elements
Subfamily True positives..
SMP_SERMA
PROTEIN TITLES
NPRE_BACCL BACILLOLYSIN PRECURSOR (EC 3.4.24.28) (THERMOSTABLE NEUTRAL
THER_BACST THERMOLYSIN PRECURSOR (EC 3.4.24.27) (THERMOSTABLE NEUTRAL P
Q59223 THERMOLYSIN PRECURSOR (EC 3.4.24.27) (THERMOSTABLE NEUTRAL P
Q59193 THERMOLYSIN PRECURSOR (EC 3.4.24.27) (THERMOSTABLE NEUTRAL P
Q43880 THERMOLYSIN PRECURSOR (EC 3.4.24.27) (THERMOSTABLE NEUTRAL P
Q48857 HYDROLASE PRECURSOR - LACTOBACILLUS SP.
NPRE_BACBR BACILLOLYSIN PRECURSOR (EC 3.4.24.28) (NEUTRAL PROTEASE) - B
NPRE_BACCE BACILLOLYSIN PRECURSOR (EC 3.4.24.28) (NEUTRAL PROTEASE) - B
O32309 NEUTRAL PROTEASE A - BACILLUS THURINGIENSIS.
NPRS_BACST BACILLOLYSIN PRECURSOR (EC 3.4.24.28) (NEUTRAL PROTEASE) - B
Q45779 THERMOLYSIN - BACILLUS THERMOPROTEOLYTICUS.
NPRM_BACME BACILLOLYSIN PRECURSOR (EC 3.4.24.28) (NEUTRAL PROTEASE) - B
NPRE_PAEPO BACILLOLYSIN PRECURSOR (EC 3.4.24.28) (NEUTRAL PROTEASE) - P
THER_BACTH THERMOLYSIN (EC 3.4.24.27) - BACILLUS THERMOPROTEOLYTICUS.
NPRE_BACAM BACILLOLYSIN PRECURSOR (EC 3.4.24.28) (NEUTRAL PROTEASE) - B
NPRE_BACSU BACILLOLYSIN PRECURSOR (EC 3.4.24.28) (NEUTRAL PROTEASE) (MC
Q44677 NEUTRAL PROTEASE - BACILLUS AMYLOLIQUEFACIENS.
PRT1_ERWCA EXTRACELLULAR METALLOPROTEASE PRECURSOR (EC 3.4.24.-) - ERWI
Q46237 LAMBDA TOXIN - CLOSTRIDIUM PERFRINGENS.
NPRB_BACSU NEUTRAL PROTEASE B PRECURSOR (EC 3.4.24.-) - BACILLUS SUBTIL
SEPA_STAEP EXTRACELLULAR ELASTASE PRECURSOR (EC 3.4.24.-) (SEPP1) - STA
AURE_STAAU ZINC METALLOPROTEINASE AUREOLYSIN (EC 3.4.24.29) (STAPHYLOCO
NPRV_VIBPR NEUTRAL PROTEASE PRECURSOR (EC 3.4.24.25) (VIBRIOLYSIN) (AER
PRO1_LISMO ZINC METALLOPROTEINASE PRECURSOR (EC 3.4.24.-) - LISTERIA MO
PRO2_LISMO ZINC METALLOPROTEINASE PRECURSOR (EC 3.4.24.-) - LISTERIA MO
EMPA_VIBAN VIRULENCE METALLOPROTEASE PRECURSOR (EC 3.4.24.-) (VIBRIOLYS
O06694 METALLOPROTEASE - VIBRIO VULNIFICUS.
P96176 NEUTRAL PROTEASE PRECURSOR (EC 3.4.24.-) (VIBRIOLYSIN) - VIB
HAPT_VIBCH HEMAGGLUTININ/PROTEINASE PRECURSOR (EC 3.4.24.-) (HA/PROTEAS
ELAS_PSEAE PSEUDOLYSIN PRECURSOR (EC 3.4.24.26) (ELASTASE) (NEUTRAL MET
PRZN_RENSA ZINC METALLOPROTEINASE PRECURSOR (EC 3.4.24.-) (HEMOLYSIN) -
PROA_LEGPN ZINC METALLOPROTEINASE PRECURSOR (EC 3.4.24.-) (PEP1) (PRO A
Q47786 GELATINASE - ENTEROCOCCUS FAECALIS (STREPTOCOCCUS FAECALIS).
PROA_LEGLO ZINC METALLOPROTEINASE PRECURSOR (EC 3.4.24.-) - LEGIONELLA
SMP_SERMA EXTRACELLULAR MINOR METALLOPROTEASE PRECURSOR (EC 3.4.24.-)
SCAN HISTORY
OWL29_1 3 100 NSINGLE
SPTR37_9f 2 36 NSINGLE
INITIAL MOTIF SETS
THERMOLYSIN1 Length of motif = 21 Motif number = 1
Thermolysin metalloprotease (M4) motif I - 1
PCODE ST INT
HYGNNYENAFWDGRAMTFGDG HAPT_VIBCH 308 308
HYGRSVENAYWDGTAMLFGDG ELAS_PSEAE 302 302
HYDSNYENAFWNGSSMTFGDG EMPA_VIBAN 311 311
HYGLNCNNAFWDGQEILYGDG PRO1_LISMO 312 312
HVGKQWNNAAWNGVQMVYGDG NPRB_BACSU 332 332
THERMOLYSIN2 Length of motif = 17 Motif number = 2
Thermolysin metalloprotease (M4) motif II - 1
PCODE ST INT
AHEVSHGFTEQNSGLVY HAPT_VIBCH 342 13
AHEVSHGFTEQNSGLIY ELAS_PSEAE 336 13
AHEVSHGFTEQNSGLVY EMPA_VIBAN 345 13
GHELTHAVIQYSAGLEY PRO1_LISMO 348 15
AHEITHAVTQYSAGLLY NPRB_BACSU 368 15
THERMOLYSIN3 Length of motif = 12 Motif number = 3
Thermolysin metalloprotease (M4) motif III - 1
PCODE ST INT
GGINEAFSDIAG HAPT_VIBCH 363 4
GGMNEAFSDMAG ELAS_PSEAE 357 4
GGINEAFSDIAG EMPA_VIBAN 366 4
GALNESFADVFG PRO1_LISMO 369 4
GALNESISDIMG NPRB_BACSU 389 4
THERMOLYSIN4 Length of motif = 17 Motif number = 4
Thermolysin metalloprotease (M4) motif IV - 1
PCODE ST INT
VHHSSGVFNRAFYLLAN HAPT_VIBCH 425 50
VHHSSGVYNRAFYLLAN ELAS_PSEAE 419 50
VHYSSGVFNRAYYLLAN EMPA_VIBAN 428 50
VHYNSGIPNKAAYNTIT PRO1_LISMO 436 55
VHINSSIHNKAAYLLAE NPRB_BACSU 452 51
FINAL MOTIF SETS
THERMOLYSIN1 Length of motif = 21 Motif number = 1
Thermolysin metalloprotease (M4) motif I - 2
PCODE ST INT
HYGRGYNNAFWNGSQMVYGDG NPRE_BACCL 333 333
HYGRGYNNAFWNGSQMVYGDG THER_BACST 337 337
HYGRGYNNAFWNGSQMVYGDG Q59223 335 335
HYGRGYNNAFWNGSQMVYGDG Q59193 335 335
HYGRGYNNAFWNGSQMVYGDG Q43880 335 335
HYGSKYNNAFWNGSQMVYGDG Q48857 355 355
HYSTRYNNAFWNGSQMVYGDG NPRE_BACBR 321 321
HYGSNYNNAFWNGSQMVYGDG NPRE_BACCE 355 355
HYGSNYNNAFWNGSQMVYGDG O32309 355 355
HYSQGYNNAFWNGSQMVYGDG NPRS_BACST 340 340
HYSQGYNNAFWNGSQMVYGDG Q45779 337 337
HYSSGYNNAFWNGSQMVYGDG NPRM_BACME 351 351
HYGSRYNNAFWNGSQMTYGDG NPRE_PAEPO 384 384
HYSQGYNNAFWNGSEMVYGDG THER_BACTH 105 105
HYGSRYNNAAWIGDQMIYGDG NPRE_BACAM 327 327
HYGTQYNNAAWTGDQMIYGDG NPRE_BACSU 327 327
QYGSRYNNAAWIGDQMIYGDG Q44677 327 327
HYGQDYQNAFWNGQQMVFGDG PRT1_ERWCA 125 125
HYGSNYNNAYWNGYKMIYGDG Q46237 337 337
HVGKQWNNAAWNGVQMVYGDG NPRB_BACSU 332 332
GGQDNRNNAAWIGDKMIYGDG AURE_STAAU 107 107
QGQDNRNNAAWIGDKMIYGDG SEPA_STAEP 314 314
HYGNNYENAFWNGSSMTFGDG NPRV_VIBPR 308 308
HYGLNCNNAFWDGQEILYGDG PRO1_LISMO 312 312
HYGLNCNNAFWDGREILYGDG PRO2_LISMO 312 312
HYDSNYENAFWNGSSMTFGDG EMPA_VIBAN 311 311
HYSSNYENAFWDGSAMTFGDG O06694 308 308
HYSSNYENAFWDGSAMTFGDG P96176 308 308
HYGNNYENAFWDGRAMTFGDG HAPT_VIBCH 308 308
HYGRSVENAYWDGTAMLFGDG ELAS_PSEAE 302 302
GEQCPFANAFWYNGQMTYGQG PRZN_RENSA 333 333
HYGQGYENAYWDGKQMTFGDG PROA_LEGPN 342 342
QHPDAYDNAFWDGKAMRYGET Q47786 290 290
HYGDGYENAYWDGEQMTFGCG PROA_LEGLO 330 330
THERMOLYSIN2 Length of motif = 17 Motif number = 2
Thermolysin metalloprotease (M4) motif II - 2
PCODE ST INT
GHELTHAVTDYTAGLVY NPRE_BACCL 369 15
GHELTHAVTDYTAGLVY THER_BACST 373 15
GHELTHAVTDYTAGLVY Q59223 371 15
GHELTHAVTDYTAGLVY Q59193 371 15
GHELTHAVTDYTAGLVY Q43880 371 15
GHELTHAVTEYSSDLIY Q48857 391 15
AHELTHAVTERTAGLVY NPRE_BACBR 357 15
GHELTHAVTENSSNLIY NPRE_BACCE 391 15
GHELTHAVTENSSNLIY O32309 391 15
AHELTHAVTDYTAGLIY NPRS_BACST 376 15
AHELTHAVTDYTAGLIY Q45779 373 15
GHELTHALTERSSNLIY NPRM_BACME 387 15
GHELTHGVTEYTSNLEY NPRE_PAEPO 422 17
AHELTHAVTDYTAGLIY THER_BACTH 141 15
AHEMTHGVTQETANLNY NPRE_BACAM 363 15
AHEMTHGVTQETANLIY NPRE_BACSU 363 15
AHEMTHGVTQETANLNY Q44677 363 15
AHELTHGITENEAGLIY PRT1_ERWCA 161 15
GHEMTHGVVTNTCNLNY Q46237 373 15
AHEITHAVTQYSAGLLY NPRB_BACSU 368 15
AHEITHGVTQQTANLEY AURE_STAAU 143 15
AHEITHGVTQQTANLVY SEPA_STAEP 350 15
AHEVSHGFTEQNSGLVY NPRV_VIBPR 342 13
GHELTHAVIQYSAGLEY PRO1_LISMO 348 15
GHELTHAVIQYSAGLEY PRO2_LISMO 348 15
AHEVSHGFTEQNSGLVY EMPA_VIBAN 345 13
AHEVSHGFTEQNSGLIY O06694 342 13
AHEVSHGFTEQNSGLIY P96176 342 13
AHEVSHGFTEQNSGLVY HAPT_VIBCH 342 13
AHEVSHGFTEQNSGLIY ELAS_PSEAE 336 13
GHELTHGVTEKTNGLVY PRZN_RENSA 361 7
GHEVSHGFTEQHSGLEY PROA_LEGPN 376 13
GHEMTHGVTEHTAGLEY Q47786 326 15
AHEISHGFTEQHSGLEY PROA_LEGLO 364 13
THERMOLYSIN3 Length of motif = 12 Motif number = 3
Thermolysin metalloprotease (M4) motif III - 2
PCODE ST INT
GAINEAMSDIFG NPRE_BACCL 390 4
GAINEAMSDIFG THER_BACST 394 4
GAINEAMSDIFG Q59223 392 4
GAINEAMSDIFG Q59193 392 4
GAINEAMSDIFG Q43880 392 4
GALNEAISDVFG Q48857 412 4
GALNESMSDIFG NPRE_BACBR 378 4
GALNEAISDIFG NPRE_BACCE 412 4
GALNEAISDIFG O32309 412 4
GAINEAISDIFG NPRS_BACST 397 4
GAINEAMSDIFG Q45779 394 4
GALNEAISDIFG NPRM_BACME 408 4
GALNEAFSDVIG NPRE_PAEPO 443 4
GAINEAISDIFG THER_BACTH 162 4
GALNESFSDVFG NPRE_BACAM 384 4
GALNESFSDVFG NPRE_BACSU 384 4
GALNESFSDVFG Q44677 384 4
GALNESLSDVFG PRT1_ERWCA 182 4
GALNESISDVFG Q46237 394 4
GALNESISDIMG NPRB_BACSU 389 4
GALNESFSDVFG AURE_STAAU 164 4
GALNESFSDVFG SEPA_STAEP 371 4
GGMNEAFSDIAG NPRV_VIBPR 363 4
GALNESFADVFG PRO1_LISMO 369 4
GALNESFADVFG PRO2_LISMO 369 4
GGINEAFSDIAG EMPA_VIBAN 366 4
GGMNEAFSDIAG O06694 363 4
GGMNEAFSDIAG P96176 363 4
GGINEAFSDIAG HAPT_VIBCH 363 4
GGMNEAFSDMAG ELAS_PSEAE 357 4
GAINESMSDVFG PRZN_RENSA 382 4
GGMNESFSDMAA PROA_LEGPN 397 4
GALNESYSDLMG Q47786 347 4
GGMNESFSDMAA PROA_LEGLO 385 4
THERMOLYSIN4 Length of motif = 17 Motif number = 4
Thermolysin metalloprotease (M4) motif IV - 2
PCODE ST INT
VHTNSGIINKAAYLLSQ NPRE_BACCL 458 56
VHTNSGIINKAAYLLSQ THER_BACST 462 56
VHTNSGIINKAAYLLSQ Q59223 460 56
VHTNSGIINKAAYLLSQ Q59193 460 56
VHTNSGIINKAAYLLSQ Q43880 460 56
VHTNSGIINKAAYLLAN Q48857 480 56
VHTNSGINNKAAYLLAE NPRE_BACBR 441 51
VHTNSGIINKQAYLLAN NPRE_BACCE 480 56
VHTNSGIINKQAYLLAN O32309 480 56
VHINSGIINKAAYLISQ NPRS_BACST 465 56
VHINSGIINKAAYLISQ Q45779 462 56
VHTNSGIINKAAYLLAN NPRM_BACME 476 56
VHTNSGIINKAYYLLAQ NPRE_PAEPO 506 51
VHINSGIINKAAYLISQ THER_BACTH 230 56
VHTNSGIPNKAAYNTIT NPRE_BACAM 448 52
VHTNSGIPNKAAYNTIT NPRE_BACSU 448 52
VHTNSGIPNKAAYNTIT Q44677 448 52
VHLNSGIPNRAFYLAAI PRT1_ERWCA 263 69
VHINSGIPNKAAYNLAS Q46237 477 71
VHINSSIHNKAAYLLAE NPRB_BACSU 452 51
VHTNSGIPNKAAYNVIQ AURE_STAAU 227 51
VHTNSGIPNKAAYNTIR SEPA_STAEP 434 51
VHYSSGVFNRAFYLLAN NPRV_VIBPR 425 50
VHYNSGIPNKAAYNTIT PRO1_LISMO 436 55
VHFNSGIPNKAAYNTIT PRO2_LISMO 436 55
VHYSSGVFNRAYYLLAN EMPA_VIBAN 428 50
VHHSSGVYNRAFYLLAN O06694 425 50
VHHSSGVYNRAFYLLAN P96176 425 50
VHHSSGVFNRAFYLLAN HAPT_VIBCH 425 50
VHHSSGVYNRAFYLLAN ELAS_PSEAE 419 50
VHSNSGVGNKLAFLITD PRZN_RENSA 458 64
VHYSSGVYNHLFYILAN PROA_LEGPN 462 53
VHYNSGIINRIGYTIIQ Q47786 417 58
VHYSSGVYNHLFYILAT PROA_LEGLO 450 53
User query: Display/Full Code "THERMOLYSIN"