WALK_STAAU
ID WALK_STAAU Reviewed; 415 AA.
AC Q9RDT3;
DT 04-NOV-2008, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 122.
DE RecName: Full=Sensor protein kinase WalK {ECO:0000305};
DE EC=2.7.13.3 {ECO:0000269|PubMed:31296851};
DE Flags: Fragment;
GN Name=walK; Synonyms=vicK, yycG;
OS Staphylococcus aureus.
OC Bacteria; Firmicutes; Bacilli; Bacillales; Staphylococcaceae;
OC Staphylococcus.
OX NCBI_TaxID=1280;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=12379689; DOI=10.1128/iai.70.11.6121-6128.2002;
RA Wagner C., de Saizieu A., Schoenfeld H.-J., Kamber M., Lange R.,
RA Thompson C.J., Page M.G.;
RT "Genetic analysis and functional characterization of the Streptococcus
RT pneumoniae vic operon.";
RL Infect. Immun. 70:6121-6128(2002).
RN [2]
RP BIOPHYSICOCHEMICAL PROPERTIES, COFACTOR, AND AUTOPHOSPHORYLATION.
RC STRAIN=WCUH29 / NCIMB 40771;
RX PubMed=12867749; DOI=10.1159/000071077;
RA Clausen V.A., Bae W., Throup J., Burnham M.K.R., Rosenberg M., Wallis N.G.;
RT "Biochemical characterization of the first essential two-component signal
RT transduction system from Staphylococcus aureus and Streptococcus
RT pneumoniae.";
RL J. Mol. Microbiol. Biotechnol. 5:252-260(2003).
RN [3]
RP OVEREXPRESSION.
RC STRAIN=SA137/93A;
RX PubMed=17418637; DOI=10.1016/j.ijmm.2007.02.002;
RA Jansen A., Tuerck M., Szekat C., Nagel M., Clever I., Bierbaum G.;
RT "Role of insertion elements and yycFG in the development of decreased
RT susceptibility to vancomycin in Staphylococcus aureus.";
RL Int. J. Med. Microbiol. 297:205-215(2007).
RN [4]
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, MUTAGENESIS OF HIS-78,
RP AND AUTOPHOSPHORYLATION.
RX PubMed=31296851; DOI=10.1038/s41467-019-10932-4;
RA Monk I.R., Shaikh N., Begg S.L., Gajdiss M., Sharkey L.K.R., Lee J.Y.H.,
RA Pidot S.J., Seemann T., Kuiper M., Winnen B., Hvorup R., Collins B.M.,
RA Bierbaum G., Udagedara S.R., Morey J.R., Pulyani N., Howden B.P.,
RA Maher M.J., McDevitt C.A., King G.F., Stinear T.P.;
RT "Zinc-binding to the cytoplasmic PAS domain regulates the essential WalK
RT histidine kinase of Staphylococcus aureus.";
RL Nat. Commun. 10:3067-3067(2019).
RN [5] {ECO:0007744|PDB:4MN5, ECO:0007744|PDB:4MN6}
RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 58-183 IN COMPLEX WITH ZINC.
RA Shaikh N., Hvorup R., Winnen B., Collins B.M., King G.F.;
RT "Crystal structure of PAS domain of S. aureus YycG.";
RL Submitted (SEP-2013) to the PDB data bank.
CC -!- FUNCTION: Member of the two-component regulatory system WalK/WalR that
CC regulates genes involved in cell wall metabolism, virulence regulation,
CC biofilm production, oxidative stress resistance and antibiotic
CC resistance via direct or indirect regulation of autolysins. Functions
CC as a sensor protein kinase which is autophosphorylated at a histidine
CC residue in the dimerization domain and transfers its phosphate group to
CC the conserved aspartic acid residue in the regulatory domain of WalR.
CC In turn, WalR binds to the upstream promoter regions of the target
CC genes to positively and negatively regulate their expression.
CC {ECO:0000269|PubMed:31296851}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + protein L-histidine = ADP + protein N-phospho-L-
CC histidine.; EC=2.7.13.3; Evidence={ECO:0000269|PubMed:31296851};
CC -!- COFACTOR:
CC Name=NH4(+); Xref=ChEBI:CHEBI:28938;
CC Evidence={ECO:0000269|PubMed:12867749};
CC -!- ACTIVITY REGULATION: By zinc. Zinc-binding negatively regulates WalK
CC kinase activity and thus autophosphorylation.
CC {ECO:0000269|PubMed:31296851}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=130 uM for ATP {ECO:0000269|PubMed:12867749};
CC Note=Kinetic parameters were determined with a truncated form of
CC WalK, which includes only the cytoplasmic domain and not the sensor
CC domain and the transmembrane region.;
CC pH dependence:
CC Optimum pH is 8.5. {ECO:0000269|PubMed:12867749};
CC -!- SUBUNIT: Forms homodimers. Forms homooligomers.
CC {ECO:0000250|UniProtKB:Q2G2U4}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000305}; Multi-pass membrane
CC protein {ECO:0000255}.
CC -!- PTM: Autophosphorylated. {ECO:0000269|PubMed:12867749,
CC ECO:0000269|PubMed:31296851}.
CC -!- MISCELLANEOUS: Overexpression of walK/walR reduces susceptibility
CC against vancomycin. {ECO:0000269|PubMed:17418637}.
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DR EMBL; AJ012052; CAB65401.1; -; Genomic_DNA.
DR PDB; 4MN5; X-ray; 2.00 A; A/B=58-183.
DR PDB; 4MN6; X-ray; 2.10 A; A/B=73-177.
DR PDB; 4YWZ; X-ray; 1.70 A; A/B=34-182.
DR PDB; 7DUC; X-ray; 2.56 A; A/B=58-183.
DR PDBsum; 4MN5; -.
DR PDBsum; 4MN6; -.
DR PDBsum; 4YWZ; -.
DR PDBsum; 7DUC; -.
DR AlphaFoldDB; Q9RDT3; -.
DR SMR; Q9RDT3; -.
DR BindingDB; Q9RDT3; -.
DR ChEMBL; CHEMBL4295968; -.
DR BRENDA; 2.7.13.3; 3352.
DR GO; GO:0016021; C:integral component of membrane; IEA:InterPro.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0000155; F:phosphorelay sensor kinase activity; IEA:InterPro.
DR CDD; cd00082; HisKA; 1.
DR CDD; cd00130; PAS; 1.
DR Gene3D; 3.30.565.10; -; 1.
DR InterPro; IPR003660; HAMP_dom.
DR InterPro; IPR003594; HATPase_C.
DR InterPro; IPR036890; HATPase_C_sf.
DR InterPro; IPR005467; His_kinase_dom.
DR InterPro; IPR003661; HisK_dim/P.
DR InterPro; IPR036097; HisK_dim/P_sf.
DR InterPro; IPR000014; PAS.
DR InterPro; IPR000700; PAS-assoc_C.
DR InterPro; IPR035965; PAS-like_dom_sf.
DR InterPro; IPR004358; Sig_transdc_His_kin-like_C.
DR Pfam; PF00672; HAMP; 1.
DR Pfam; PF02518; HATPase_c; 1.
DR Pfam; PF00512; HisKA; 1.
DR Pfam; PF13426; PAS_9; 1.
DR PRINTS; PR00344; BCTRLSENSOR.
DR SMART; SM00304; HAMP; 1.
DR SMART; SM00387; HATPase_c; 1.
DR SMART; SM00388; HisKA; 1.
DR SMART; SM00091; PAS; 1.
DR SUPFAM; SSF47384; SSF47384; 1.
DR SUPFAM; SSF55785; SSF55785; 1.
DR SUPFAM; SSF55874; SSF55874; 1.
DR TIGRFAMs; TIGR00229; sensory_box; 1.
DR PROSITE; PS50885; HAMP; 1.
DR PROSITE; PS50109; HIS_KIN; 1.
DR PROSITE; PS50113; PAC; 1.
DR PROSITE; PS50112; PAS; 1.
PE 1: Evidence at protein level;
KW 3D-structure; ATP-binding; Cell membrane; Kinase; Membrane; Metal-binding;
KW Nucleotide-binding; Phosphoprotein; Transferase;
KW Two-component regulatory system; Zinc.
FT CHAIN <1..415
FT /note="Sensor protein kinase WalK"
FT /id="PRO_0000353050"
FT DOMAIN 11..63
FT /note="HAMP"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00102"
FT DOMAIN 68..138
FT /note="PAS"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00140"
FT DOMAIN 121..185
FT /note="PAC"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00141"
FT DOMAIN 189..407
FT /note="Histidine kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00107"
FT BINDING 78
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000269|PubMed:31296851, ECO:0000269|Ref.5,
FT ECO:0007744|PDB:4MN5, ECO:0007744|PDB:4MN6"
FT BINDING 81
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000269|PubMed:31296851, ECO:0000269|Ref.5,
FT ECO:0007744|PDB:4MN5, ECO:0007744|PDB:4MN6"
FT BINDING 171
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000269|PubMed:31296851, ECO:0000269|Ref.5,
FT ECO:0007744|PDB:4MN5, ECO:0007744|PDB:4MN6"
FT BINDING 175
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000269|PubMed:31296851, ECO:0000269|Ref.5,
FT ECO:0007744|PDB:4MN5, ECO:0007744|PDB:4MN6"
FT MOD_RES 192
FT /note="Phosphohistidine; by autocatalysis"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00107"
FT MUTAGEN 78
FT /note="H->Y: Complete loss of metal binding."
FT /evidence="ECO:0000269|PubMed:31296851"
FT NON_TER 1
FT STRAND 82..86
FT /evidence="ECO:0007829|PDB:4MN5"
FT STRAND 91..95
FT /evidence="ECO:0007829|PDB:4MN5"
FT HELIX 97..103
FT /evidence="ECO:0007829|PDB:4MN5"
FT HELIX 107..109
FT /evidence="ECO:0007829|PDB:4MN5"
FT TURN 110..112
FT /evidence="ECO:0007829|PDB:4MN5"
FT HELIX 115..118
FT /evidence="ECO:0007829|PDB:4MN5"
FT TURN 122..124
FT /evidence="ECO:0007829|PDB:4MN5"
FT HELIX 127..129
FT /evidence="ECO:0007829|PDB:4MN5"
FT TURN 130..132
FT /evidence="ECO:0007829|PDB:4MN5"
FT STRAND 137..140
FT /evidence="ECO:0007829|PDB:4MN5"
FT TURN 143..145
FT /evidence="ECO:0007829|PDB:7DUC"
FT STRAND 148..157
FT /evidence="ECO:0007829|PDB:4MN5"
FT STRAND 163..172
FT /evidence="ECO:0007829|PDB:4MN5"
SQ SEQUENCE 415 AA; 47818 MW; 8900B32BD63BFC4B CRC64;
CTVILGFFIA RTITKPITDM RNQTVEMSRG NYTQRVKIYG NDEIGELALA FNNLSKRVQE
AQANTESEKR RLDSVITHMS DGIIATDRRG RIRIVNDMAL KMLGMAKEDI IGYYMLSVLS
LEDEFKLEEI QENNDSFLLD LNEEEGLIAR VNFSTIVQET GFVTGYIAVL HDVTEQQQVE
RERREFVANV SHELRTPLTS MNSYIEALEE GAWKDEELAP QFLSVTREET ERMIRLVNDL
LQLSKMDNES DQINKEIIDF NMFINKIINR HEMSAKDTTF IRDIPKKTIF TEFDPDKMTQ
VFDNVITNAM KYSRGDKRVE FHVKQNPLYN RMTIRIKDNG IGIPINKVDK IFDRFYRVDK
ARTRKMGGTG LGLAISKEIV EAHNGRIWAN SVEGQGTSIF ITLPCEVIED GDWDE
