AURE_STAAU
ID AURE_STAAU Reviewed; 509 AA.
AC P81177; Q9R2Z8;
DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2000, sequence version 2.
DT 03-AUG-2022, entry version 117.
DE RecName: Full=Zinc metalloproteinase aureolysin {ECO:0000303|PubMed:9753696};
DE EC=3.4.24.29 {ECO:0000269|PubMed:17878159};
DE AltName: Full=Staphylococcus aureus neutral proteinase;
DE Flags: Precursor;
GN Name=aur {ECO:0000303|PubMed:10639475};
OS Staphylococcus aureus.
OC Bacteria; Firmicutes; Bacilli; Bacillales; Staphylococcaceae;
OC Staphylococcus.
OX NCBI_TaxID=1280;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=022, and V8-BC10;
RX PubMed=10639475; DOI=10.1128/iai.68.2.973-976.2000;
RA Sabat A., Kosowska K., Poulsen K., Kasprowicz A., Sekowska A.,
RA van Den Burg B., Travis J., Potempa J.;
RT "Two allelic forms of the aureolysin gene (aur) within Staphylococcus
RT aureus.";
RL Infect. Immun. 68:973-976(2000).
RN [2] {ECO:0007744|PDB:1BQB}
RP PROTEIN SEQUENCE OF 209-509, X-RAY CRYSTALLOGRAPHY (1.72 ANGSTROMS) OF
RP 209-509 IN COMPLEX WITH CALCIUM AND ZINC, PROBABLE ACTIVE SITE, COFACTOR,
RP AND SUBUNIT.
RC STRAIN=ATCC 27733 / V8;
RX PubMed=9753696; DOI=10.1016/s0969-2126(98)00118-x;
RA Banbula A., Potempa J., Travis J., Fernandez-Catalan C., Mann K., Huber R.,
RA Bode W., Medrano F.J.;
RT "Amino-acid sequence and three-dimensional structure of the Staphylococcus
RT aureus metalloproteinase at 1.72-A resolution.";
RL Structure 6:1185-1193(1998).
RN [3]
RP FUNCTION.
RX PubMed=3533918; DOI=10.1016/s0021-9258(18)67022-x;
RA Potempa J., Watorek W., Travis J.;
RT "The inactivation of human plasma alpha 1-proteinase inhibitor by
RT proteinases from Staphylococcus aureus.";
RL J. Biol. Chem. 261:14330-14334(1986).
RN [4]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RC STRAIN=UAMS-1182;
RX PubMed=17878159; DOI=10.1074/jbc.m705672200;
RA Nickerson N.N., Prasad L., Jacob L., Delbaere L.T., McGavin M.J.;
RT "Activation of the SspA serine protease zymogen of Staphylococcus aureus
RT proceeds through unique variations of a trypsinogen-like mechanism and is
RT dependent on both autocatalytic and metalloprotease-specific processing.";
RL J. Biol. Chem. 282:34129-34138(2007).
RN [5]
RP FUNCTION.
RC STRAIN=UAMS-1182;
RX PubMed=21502375; DOI=10.4049/jimmunol.1002948;
RA Laarman A.J., Ruyken M., Malone C.L., van Strijp J.A., Horswill A.R.,
RA Rooijakkers S.H.;
RT "Staphylococcus aureus metalloprotease aureolysin cleaves complement C3 to
RT mediate immune evasion.";
RL J. Immunol. 186:6445-6453(2011).
CC -!- FUNCTION: Plays an essential role in immune evasion by helping bacteria
CC to resist complement-mediated killing by neutrophils. Inhibits the
CC deposition of host C3b on bacterial surfaces and the release of the
CC chemoattractant C5a by cleaving the central complement protein C3. The
CC cleavage site renders the C3b molecule vulnerable to proteolytic
CC degradation by host regulators (PubMed:21502375). Cleaves and
CC inactivates host SERPINA1, which is an endogenous protease inhibitor
CC essential for controlling neutrophil serine protease elastase
CC (PubMed:3533918). Also plays an essential role in the cleavage and
CC subsequent activation of the serine protease SspA (glutamyl
CC endopeptidase) which is involved in colonization and infection of human
CC tissues (PubMed:17878159). {ECO:0000269|PubMed:17878159,
CC ECO:0000269|PubMed:21502375, ECO:0000269|PubMed:3533918}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Cleavage of insulin B chain with specificity similar to that
CC of thermolysin, preferring hydrophobic P1' residues. Activates the
CC glutamyl endopeptidase (EC 3.4.21.19) of Staphylococcus aureus.;
CC EC=3.4.24.29; Evidence={ECO:0000269|PubMed:17878159};
CC -!- COFACTOR:
CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108;
CC Evidence={ECO:0000269|PubMed:9753696, ECO:0007744|PDB:1BQB};
CC Note=Binds 3 Ca(2+) ions per subunit. {ECO:0000269|PubMed:9753696,
CC ECO:0007744|PDB:1BQB};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000269|PubMed:9753696, ECO:0007744|PDB:1BQB};
CC Note=Binds 1 zinc ion per subunit. {ECO:0000269|PubMed:9753696,
CC ECO:0007744|PDB:1BQB};
CC -!- SUBUNIT: Monomer. {ECO:0000305|PubMed:9753696}.
CC -!- SIMILARITY: Belongs to the peptidase M4 family. {ECO:0000305}.
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DR EMBL; AJ249166; CAB59567.1; -; Genomic_DNA.
DR EMBL; AJ249167; CAB59568.1; -; Genomic_DNA.
DR RefSeq; WP_001225040.1; NZ_VSSN01000014.1.
DR PDB; 1BQB; X-ray; 1.72 A; A=209-509.
DR PDB; 7SKL; X-ray; 1.60 A; A/C=209-509.
DR PDB; 7SKM; X-ray; 1.85 A; A/C=209-509.
DR PDBsum; 1BQB; -.
DR PDBsum; 7SKL; -.
DR PDBsum; 7SKM; -.
DR AlphaFoldDB; P81177; -.
DR SMR; P81177; -.
DR MEROPS; M04.009; -.
DR OMA; WKHIKLT; -.
DR BRENDA; 3.4.24.29; 3352.
DR EvolutionaryTrace; P81177; -.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004222; F:metalloendopeptidase activity; IEA:InterPro.
DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR Gene3D; 1.10.390.10; -; 1.
DR InterPro; IPR011096; FTP_domain.
DR InterPro; IPR025711; PepSY.
DR InterPro; IPR023612; Peptidase_M4.
DR InterPro; IPR027268; Peptidase_M4/M1_CTD_sf.
DR InterPro; IPR001570; Peptidase_M4_C_domain.
DR InterPro; IPR013856; Peptidase_M4_domain.
DR Pfam; PF07504; FTP; 1.
DR Pfam; PF03413; PepSY; 1.
DR Pfam; PF01447; Peptidase_M4; 1.
DR Pfam; PF02868; Peptidase_M4_C; 1.
DR PRINTS; PR00730; THERMOLYSIN.
DR PROSITE; PS00142; ZINC_PROTEASE; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Calcium; Direct protein sequencing; Hydrolase; Metal-binding;
KW Metalloprotease; Protease; Signal; Virulence; Zinc; Zymogen.
FT SIGNAL 1..27
FT /evidence="ECO:0000255"
FT PROPEP 28..208
FT /evidence="ECO:0000269|PubMed:9753696"
FT /id="PRO_0000028614"
FT CHAIN 209..509
FT /note="Zinc metalloproteinase aureolysin"
FT /id="PRO_0000028615"
FT ACT_SITE 353
FT /evidence="ECO:0000305|PubMed:9753696"
FT ACT_SITE 436
FT /note="Proton donor"
FT BINDING 348
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:9753696,
FT ECO:0007744|PDB:1BQB"
FT BINDING 352
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000269|PubMed:9753696,
FT ECO:0007744|PDB:1BQB"
FT BINDING 356
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000269|PubMed:9753696,
FT ECO:0007744|PDB:1BQB"
FT BINDING 376
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000269|PubMed:9753696,
FT ECO:0007744|PDB:1BQB"
FT BINDING 387
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:9753696,
FT ECO:0007744|PDB:1BQB"
FT BINDING 387
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:9753696,
FT ECO:0007744|PDB:1BQB"
FT BINDING 389
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:9753696,
FT ECO:0007744|PDB:1BQB"
FT BINDING 390
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:9753696,
FT ECO:0007744|PDB:1BQB"
FT BINDING 390
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:9753696,
FT ECO:0007744|PDB:1BQB"
FT BINDING 392
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:9753696,
FT ECO:0007744|PDB:1BQB"
FT BINDING 395
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:9753696,
FT ECO:0007744|PDB:1BQB"
FT BINDING 395
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:9753696,
FT ECO:0007744|PDB:1BQB"
FT BINDING 398
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000269|PubMed:9753696,
FT ECO:0007744|PDB:1BQB"
FT BINDING 399
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000269|PubMed:9753696,
FT ECO:0007744|PDB:1BQB"
FT BINDING 402
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000269|PubMed:9753696,
FT ECO:0007744|PDB:1BQB"
FT BINDING 405
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000269|PubMed:9753696,
FT ECO:0007744|PDB:1BQB"
FT CONFLICT 354
FT /note="L -> I (in Ref. 2; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 361
FT /note="E -> Q (in Ref. 2; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 479
FT /note="C -> L (in Ref. 2; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 492..493
FT /note="DE -> EQ (in Ref. 2; AA sequence)"
FT /evidence="ECO:0000305"
FT STRAND 210..216
FT /evidence="ECO:0007829|PDB:7SKL"
FT STRAND 222..230
FT /evidence="ECO:0007829|PDB:7SKL"
FT STRAND 233..238
FT /evidence="ECO:0007829|PDB:7SKL"
FT STRAND 240..243
FT /evidence="ECO:0007829|PDB:7SKL"
FT STRAND 245..251
FT /evidence="ECO:0007829|PDB:7SKL"
FT TURN 252..255
FT /evidence="ECO:0007829|PDB:7SKL"
FT STRAND 256..259
FT /evidence="ECO:0007829|PDB:7SKL"
FT STRAND 261..267
FT /evidence="ECO:0007829|PDB:7SKL"
FT HELIX 270..272
FT /evidence="ECO:0007829|PDB:7SKL"
FT HELIX 273..293
FT /evidence="ECO:0007829|PDB:7SKL"
FT STRAND 305..310
FT /evidence="ECO:0007829|PDB:7SKL"
FT STRAND 313..318
FT /evidence="ECO:0007829|PDB:7SKL"
FT STRAND 323..325
FT /evidence="ECO:0007829|PDB:7SKL"
FT STRAND 327..332
FT /evidence="ECO:0007829|PDB:7SKL"
FT STRAND 337..341
FT /evidence="ECO:0007829|PDB:7SKL"
FT HELIX 343..345
FT /evidence="ECO:0007829|PDB:7SKL"
FT HELIX 347..361
FT /evidence="ECO:0007829|PDB:7SKL"
FT HELIX 369..386
FT /evidence="ECO:0007829|PDB:7SKL"
FT STRAND 391..394
FT /evidence="ECO:0007829|PDB:7SKL"
FT TURN 395..397
FT /evidence="ECO:0007829|PDB:7SKL"
FT STRAND 398..401
FT /evidence="ECO:0007829|PDB:7SKM"
FT STRAND 407..411
FT /evidence="ECO:0007829|PDB:7SKL"
FT HELIX 413..416
FT /evidence="ECO:0007829|PDB:7SKL"
FT HELIX 422..424
FT /evidence="ECO:0007829|PDB:7SKL"
FT HELIX 431..438
FT /evidence="ECO:0007829|PDB:7SKL"
FT HELIX 440..453
FT /evidence="ECO:0007829|PDB:7SKL"
FT HELIX 455..468
FT /evidence="ECO:0007829|PDB:7SKL"
FT HELIX 476..490
FT /evidence="ECO:0007829|PDB:7SKL"
FT HELIX 493..504
FT /evidence="ECO:0007829|PDB:7SKL"
FT TURN 505..507
FT /evidence="ECO:0007829|PDB:7SKL"
SQ SEQUENCE 509 AA; 56321 MW; C622D5B7228108E5 CRC64;
MRKFSRYAFT SMATVTLLSS LTPAALASDT NHKPATSDIN FEITQKSDAV KALKELPKSE
NVKNHYQDYS VTDVKTDKKG FTHYTLQPSV DGVHAPDKEV KVHADKSGKV VLINGDTDAK
KVKPTNKVTL SKDEAADKAF NAVKIDKNKA KNLQDDVIKE NKVEIDGDSN KYIYNIELIT
VTPEISHWKV KIDADTGAVV EKTNLVKEAA ATGTGKGVLG DTKDININSI DGGFSLEDLT
HQGKLSAYNF NDQTGQATLI TNEDENFVKD DQRAGVDANY YAKQTYDYYK NTFGRESYDN
HGSPIVSLTH VNHYGGQDNR NNAAWIGDKM IYGDGDGRTF TNLSGANDVV AHELTHGVTQ
ETANLEYKDQ SGALNESFSD VFGYFVDDED FLMGEDVYTP GKEGDALRSM SNPEQFGQPS
HMKDYVYTEK DNGGVHTNSG IPNKAAYNVI QAIGKSKSEQ IYYRALTEYL TSNSNFKDCK
DALYQAAKDL YDEQTAEQVY EAWNEVGVE
