ID   DGCZ_ECOLI              Reviewed;         296 AA.
AC   P31129; P76152; P77452;
DT   01-JUL-1993, integrated into UniProtKB/Swiss-Prot.
DT   15-JUL-1998, sequence version 2.
DT   27-MAR-2024, entry version 165.
DE   RecName: Full=Diguanylate cyclase DgcZ {ECO:0000303|PubMed:23769666};
DE            Short=DGC {ECO:0000303|PubMed:18713317};
DE            EC=2.7.7.65 {ECO:0000269|PubMed:19460094, ECO:0000269|PubMed:20582742, ECO:0000305|PubMed:18713317};
DE   AltName: Full=Zinc-sensory diguanylate cyclase {ECO:0000303|PubMed:23769666};
GN   Name=dgcZ {ECO:0000303|PubMed:23769666, ECO:0000303|PubMed:26148715};
GN   Synonyms=ydeG, ydeH; OrderedLocusNames=b1535, JW1528;
OS   Escherichia coli (strain K12).
OC   Bacteria; Pseudomonadota; Gammaproteobacteria; Enterobacterales;
OC   Enterobacteriaceae; Escherichia.
OX   NCBI_TaxID=83333;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=8383113; DOI=10.1128/jb.175.5.1484-1492.1993;
RA   Cohen S.P., Haechler H., Levy S.B.;
RT   "Genetic and functional analysis of the multiple antibiotic resistance
RT   (mar) locus in Escherichia coli.";
RL   J. Bacteriol. 175:1484-1492(1993).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=K12 / W3110 / ATCC 27325 / DSM 5911;
RX   PubMed=9097039; DOI=10.1093/dnares/3.6.363;
RA   Aiba H., Baba T., Fujita K., Hayashi K., Inada T., Isono K., Itoh T.,
RA   Kasai H., Kashimoto K., Kimura S., Kitakawa M., Kitagawa M., Makino K.,
RA   Miki T., Mizobuchi K., Mori H., Mori T., Motomura K., Nakade S.,
RA   Nakamura Y., Nashimoto H., Nishio Y., Oshima T., Saito N., Sampei G.,
RA   Seki Y., Sivasundaram S., Tagami H., Takeda J., Takemoto K., Takeuchi Y.,
RA   Wada C., Yamamoto Y., Horiuchi T.;
RT   "A 570-kb DNA sequence of the Escherichia coli K-12 genome corresponding to
RT   the 28.0-40.1 min region on the linkage map.";
RL   DNA Res. 3:363-377(1996).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=K12 / MG1655 / ATCC 47076;
RX   PubMed=9278503; DOI=10.1126/science.277.5331.1453;
RA   Blattner F.R., Plunkett G. III, Bloch C.A., Perna N.T., Burland V.,
RA   Riley M., Collado-Vides J., Glasner J.D., Rode C.K., Mayhew G.F.,
RA   Gregor J., Davis N.W., Kirkpatrick H.A., Goeden M.A., Rose D.J., Mau B.,
RA   Shao Y.;
RT   "The complete genome sequence of Escherichia coli K-12.";
RL   Science 277:1453-1462(1997).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=K12 / W3110 / ATCC 27325 / DSM 5911;
RX   PubMed=16738553; DOI=10.1038/msb4100049;
RA   Hayashi K., Morooka N., Yamamoto Y., Fujita K., Isono K., Choi S.,
RA   Ohtsubo E., Baba T., Wanner B.L., Mori H., Horiuchi T.;
RT   "Highly accurate genome sequences of Escherichia coli K-12 strains MG1655
RT   and W3110.";
RL   Mol. Syst. Biol. 2:E1-E5(2006).
RN   [5]
RP   PROBABLE ENZYME ACTIVITY, MUTAGENESIS OF 206-GLY-GLY-207, DISRUPTION
RP   PHENOTYPE, AND POST-TRANSCRIPTIONAL REGULATION BY CSRA.
RC   STRAIN=K12;
RX   PubMed=18713317; DOI=10.1111/j.1365-2958.2008.06411.x;
RA   Jonas K., Edwards A.N., Simm R., Romeo T., Romling U., Melefors O.;
RT   "The RNA binding protein CsrA controls cyclic di-GMP metabolism by directly
RT   regulating the expression of GGDEF proteins.";
RL   Mol. Microbiol. 70:236-257(2008).
RN   [6]
RP   INDUCTION, AND RPOS-REPRESSION.
RC   STRAIN=K12 / W3110 / ATCC 27325 / DSM 5911;
RX   PubMed=19332833; DOI=10.1099/mic.0.024257-0;
RA   Sommerfeldt N., Possling A., Becker G., Pesavento C., Tschowri N.,
RA   Hengge R.;
RT   "Gene expression patterns and differential input into curli fimbriae
RT   regulation of all GGDEF/EAL domain proteins in Escherichia coli.";
RL   Microbiology 155:1318-1331(2009).
RN   [7]
RP   FUNCTION IN BIOFILM FORMATION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL
RP   PROPERTIES, ACTIVITY REGULATION, SUBUNIT, MUTAGENESIS OF GLU-208, AND
RP   DISRUPTION PHENOTYPE.
RC   STRAIN=K12 / AB400;
RX   PubMed=19460094; DOI=10.1111/j.1365-2958.2009.06739.x;
RA   Boehm A., Steiner S., Zaehringer F., Casanova A., Hamburger F., Ritz D.,
RA   Keck W., Ackermann M., Schirmer T., Jenal U.;
RT   "Second messenger signalling governs Escherichia coli biofilm induction
RT   upon ribosomal stress.";
RL   Mol. Microbiol. 72:1500-1516(2009).
RN   [8]
RP   FUNCTION, CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX   PubMed=20582742; DOI=10.1007/s12010-010-9017-x;
RA   Zaehringer F., Massa C., Schirmer T.;
RT   "Efficient enzymatic production of the bacterial second messenger c-di-GMP
RT   by the diguanylate cyclase YdeH from E. coli.";
RL   Appl. Biochem. Biotechnol. 163:71-79(2011).
RN   [9]
RP   NOMENCLATURE.
RX   PubMed=26148715; DOI=10.1128/jb.00424-15;
RA   Hengge R., Galperin M.Y., Ghigo J.M., Gomelsky M., Green J., Hughes K.T.,
RA   Jenal U., Landini P.;
RT   "Systematic nomenclature for GGDEF and EAL domain-containing cyclic di-GMP
RT   turnover proteins of Escherichia coli.";
RL   J. Bacteriol. 198:7-11(2015).
RN   [10] {ECO:0007744|PDB:3T9O, ECO:0007744|PDB:3TVK, ECO:0007744|PDB:4H54}
RP   X-RAY CRYSTALLOGRAPHY (1.80 ANGSTROMS) OF 127-296 IN COMPLEXES WITH CYCLIC
RP   DIGUANOSINE MONOPHOSPHATE; MAGNESIUM AND ZINC, FUNCTION, NOMENCLATURE,
RP   COFACTOR, ACTIVITY REGULATION, SUBUNIT, DOMAIN, AND MUTAGENESIS OF CYS-52;
RP   HIS-79 AND HIS-83.
RX   PubMed=23769666; DOI=10.1016/j.str.2013.04.026;
RA   Zahringer F., Lacanna E., Jenal U., Schirmer T., Boehm A.;
RT   "Structure and signaling mechanism of a zinc-sensory diguanylate cyclase.";
RL   Structure 21:1149-1157(2013).
CC   -!- FUNCTION: Catalyzes the synthesis of cyclic-di-GMP (c-di-GMP) via the
CC       condensation of 2 GTP molecules (PubMed:18713317, PubMed:19460094,
CC       PubMed:20582742). May act as a zinc sensor that controls, via c-di-GMP,
CC       post-translational events (PubMed:23769666). Overexpression leads to a
CC       strong repression of swimming; swimming returnes to normal when
CC       residues 206-207 are both mutated to Ala. Overexpression also leads to
CC       a reduction in flagellar abundance and a 20-fold increase in c-di-GMP
CC       levels in vivo. Required for aminoglycoside-mediated induction of
CC       biofilm formation, it also plays a lesser role in biofilm production in
CC       response to other classes of translation inhibitors. The c-di-GMP
CC       produced by this enzyme up-regulates poly-GlcNAc production as well as
CC       the biofilm synthesis protein PgaD, although c-di-GMP is probably not
CC       the main inducing principle. C-di-GMP is a second messenger which
CC       controls cell surface-associated traits in bacteria (PubMed:19460094).
CC       {ECO:0000269|PubMed:19460094, ECO:0000269|PubMed:20582742,
CC       ECO:0000269|PubMed:23769666, ECO:0000305|PubMed:18713317}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=2 GTP = 3',3'-c-di-GMP + 2 diphosphate; Xref=Rhea:RHEA:24898,
CC         ChEBI:CHEBI:33019, ChEBI:CHEBI:37565, ChEBI:CHEBI:58805; EC=2.7.7.65;
CC         Evidence={ECO:0000269|PubMed:19460094, ECO:0000269|PubMed:20582742,
CC         ECO:0000305|PubMed:18713317};
CC   -!- COFACTOR:
CC       Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC         Evidence={ECO:0000269|PubMed:23769666};
CC       Note=Binds 1 Mg(2+) ion per monomer. {ECO:0000269|PubMed:23769666};
CC   -!- ACTIVITY REGULATION: Allosterically regulated by zinc, which seems to
CC       regulate the activity of the catalytic GGDEF domains by impeding their
CC       mobility and thus preventing productive encounter of the two GTP
CC       substrates (PubMed:23769666). Subject to product inhibition by c-di-GMP
CC       at a KI of 44 uM (PubMed:19460094). {ECO:0000269|PubMed:19460094,
CC       ECO:0000269|PubMed:23769666}.
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       Kinetic parameters:
CC         KM=17 uM for GTP {ECO:0000269|PubMed:19460094};
CC       pH dependence:
CC         Optimum pH is 7.5. {ECO:0000269|PubMed:20582742};
CC   -!- PATHWAY: Purine metabolism; 3',5'-cyclic di-GMP biosynthesis.
CC       {ECO:0000305}.
CC   -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:19460094,
CC       ECO:0000269|PubMed:23769666}.
CC   -!- INTERACTION:
CC       P31129; P31129: dgcZ; NbExp=3; IntAct=EBI-1124405, EBI-1124405;
CC   -!- INDUCTION: CsrA binds to the mRNA and reduces its levels. Expressed at
CC       low levels at both 28 and 37 degrees Celsius. Repressed by RpoS.
CC       {ECO:0000269|PubMed:18713317, ECO:0000269|PubMed:19332833}.
CC   -!- DOMAIN: Contains an N-terminal CZB (chemoreceptor zinc binding) domain
CC       and a C-terminal GGDEF domain. {ECO:0000269|PubMed:23769666}.
CC   -!- DISRUPTION PHENOTYPE: A slight increase in motility. No visible effect
CC       on curli production (PubMed:18713317). Decreased biofilm formation,
CC       very little associated poly-GlcNAc production, and a complete loss of
CC       aminoglycoside-mediated induction of biofilm formation
CC       (PubMed:19460094). {ECO:0000269|PubMed:18713317,
CC       ECO:0000269|PubMed:19460094}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=M96235; Type=Frameshift; Evidence={ECO:0000305};
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DR   EMBL; M96235; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; U00096; AAC74608.1; -; Genomic_DNA.
DR   EMBL; AP009048; BAA18882.2; -; Genomic_DNA.
DR   PIR; B64908; B64908.
DR   RefSeq; NP_416052.1; NC_000913.3.
DR   RefSeq; WP_000592814.1; NZ_SSZK01000001.1.
DR   PDB; 3T9O; X-ray; 2.20 A; A/B=2-126.
DR   PDB; 3TVK; X-ray; 1.80 A; A=127-296.
DR   PDB; 4H54; X-ray; 3.90 A; A/B=2-296.
DR   PDBsum; 3T9O; -.
DR   PDBsum; 3TVK; -.
DR   PDBsum; 4H54; -.
DR   AlphaFoldDB; P31129; -.
DR   SMR; P31129; -.
DR   BioGRID; 4259114; 10.
DR   DIP; DIP-11677N; -.
DR   IntAct; P31129; 6.
DR   STRING; 511145.b1535; -.
DR   PaxDb; 511145-b1535; -.
DR   EnsemblBacteria; AAC74608; AAC74608; b1535.
DR   GeneID; 946075; -.
DR   KEGG; ecj:JW1528; -.
DR   KEGG; eco:b1535; -.
DR   PATRIC; fig|511145.12.peg.1605; -.
DR   EchoBASE; EB1596; -.
DR   eggNOG; COG3706; Bacteria.
DR   HOGENOM; CLU_000445_11_5_6; -.
DR   InParanoid; P31129; -.
DR   OMA; NIRSNMD; -.
DR   OrthoDB; 9812260at2; -.
DR   PhylomeDB; P31129; -.
DR   BioCyc; EcoCyc:EG11643-MONOMER; -.
DR   BioCyc; MetaCyc:EG11643-MONOMER; -.
DR   BRENDA; 2.7.7.65; 2026.
DR   SABIO-RK; P31129; -.
DR   UniPathway; UPA00599; -.
DR   PRO; PR:P31129; -.
DR   Proteomes; UP000000318; Chromosome.
DR   Proteomes; UP000000625; Chromosome.
DR   GO; GO:0060187; C:cell pole; IDA:EcoCyc.
DR   GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR   GO; GO:0052621; F:diguanylate cyclase activity; IDA:EcoCyc.
DR   GO; GO:0005525; F:GTP binding; IEA:UniProtKB-KW.
DR   GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR   GO; GO:0042803; F:protein homodimerization activity; IDA:EcoCyc.
DR   GO; GO:0008270; F:zinc ion binding; IDA:EcoCyc.
DR   GO; GO:0043709; P:cell adhesion involved in single-species biofilm formation; IMP:EcoCyc.
DR   GO; GO:0008152; P:metabolic process; IEA:UniProtKB-KW.
DR   GO; GO:1902209; P:negative regulation of bacterial-type flagellum assembly; IMP:EcoCyc.
DR   GO; GO:1902201; P:negative regulation of bacterial-type flagellum-dependent cell motility; IBA:GO_Central.
DR   GO; GO:1900233; P:positive regulation of single-species biofilm formation on inanimate substrate; IMP:EcoCyc.
DR   CDD; cd01949; GGDEF; 1.
DR   Gene3D; 3.30.70.270; -; 1.
DR   Gene3D; 1.20.120.30; Aspartate receptor, ligand-binding domain; 1.
DR   InterPro; IPR000160; GGDEF_dom.
DR   InterPro; IPR029787; Nucleotide_cyclase.
DR   InterPro; IPR043128; Rev_trsase/Diguanyl_cyclase.
DR   NCBIfam; TIGR00254; GGDEF; 1.
DR   PANTHER; PTHR45138:SF30; DIGUANYLATE CYCLASE DGCZ; 1.
DR   PANTHER; PTHR45138; REGULATORY COMPONENTS OF SENSORY TRANSDUCTION SYSTEM; 1.
DR   Pfam; PF00990; GGDEF; 1.
DR   SMART; SM00267; GGDEF; 1.
DR   SUPFAM; SSF55073; Nucleotide cyclase; 1.
DR   PROSITE; PS50887; GGDEF; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Allosteric enzyme; GTP-binding; Magnesium; Metal-binding;
KW   Nucleotide-binding; Reference proteome; Transferase.
FT   CHAIN           1..296
FT                   /note="Diguanylate cyclase DgcZ"
FT                   /id="PRO_0000168946"
FT   DOMAIN          157..289
FT                   /note="GGDEF"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00095"
FT   ACT_SITE        208
FT                   /note="Proton acceptor"
FT                   /evidence="ECO:0000255"
FT   BINDING         22
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /evidence="ECO:0000269|PubMed:23769666,
FT                   ECO:0007744|PDB:3T9O, ECO:0007744|PDB:4H54"
FT   BINDING         52
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /evidence="ECO:0000269|PubMed:23769666,
FT                   ECO:0007744|PDB:3T9O"
FT   BINDING         79
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /evidence="ECO:0000269|PubMed:23769666,
FT                   ECO:0007744|PDB:3T9O, ECO:0007744|PDB:4H54"
FT   BINDING         83
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /evidence="ECO:0000269|PubMed:23769666,
FT                   ECO:0007744|PDB:3T9O, ECO:0007744|PDB:4H54"
FT   BINDING         165
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /evidence="ECO:0000269|PubMed:23769666,
FT                   ECO:0007744|PDB:4H54"
FT   BINDING         166
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /evidence="ECO:0000269|PubMed:23769666,
FT                   ECO:0007744|PDB:4H54"
FT   BINDING         173
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000305|PubMed:23769666"
FT   BINDING         178
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000305|PubMed:23769666"
FT   BINDING         182
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000305|PubMed:23769666"
FT   BINDING         195..200
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000305|PubMed:23769666"
FT   BINDING         208
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /evidence="ECO:0000269|PubMed:23769666,
FT                   ECO:0007744|PDB:4H54"
FT   BINDING         215
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000305|PubMed:23769666"
FT   BINDING         224
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000305|PubMed:23769666"
FT   BINDING         228
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000305|PubMed:23769666"
FT   SITE            170
FT                   /note="Transition state stabilizer"
FT                   /evidence="ECO:0000255"
FT   MUTAGEN         52
FT                   /note="C->A: Decreases zinc affinity by one order of
FT                   magnitude."
FT                   /evidence="ECO:0000269|PubMed:23769666"
FT   MUTAGEN         79
FT                   /note="H->L: Displays constitutively high biofilm and PgaD
FT                   levels; when associated with L-83."
FT                   /evidence="ECO:0000269|PubMed:23769666"
FT   MUTAGEN         83
FT                   /note="H->L: Displays constitutively high biofilm and PgaD
FT                   levels; when associated with L-79."
FT                   /evidence="ECO:0000269|PubMed:23769666"
FT   MUTAGEN         206..207
FT                   /note="GG->AA: Cells overexpressing this mutant are no
FT                   longer swimming suppressed."
FT                   /evidence="ECO:0000269|PubMed:18713317"
FT   MUTAGEN         208
FT                   /note="E->Q: Significantly decreased biofilm formation."
FT                   /evidence="ECO:0000269|PubMed:19460094"
FT   HELIX           6..35
FT                   /evidence="ECO:0007829|PDB:3T9O"
FT   HELIX           41..44
FT                   /evidence="ECO:0007829|PDB:3T9O"
FT   HELIX           48..50
FT                   /evidence="ECO:0007829|PDB:3T9O"
FT   HELIX           53..59
FT                   /evidence="ECO:0007829|PDB:3T9O"
FT   TURN            66..68
FT                   /evidence="ECO:0007829|PDB:3T9O"
FT   HELIX           69..94
FT                   /evidence="ECO:0007829|PDB:3T9O"
FT   HELIX           100..125
FT                   /evidence="ECO:0007829|PDB:3T9O"
FT   TURN            133..135
FT                   /evidence="ECO:0007829|PDB:3TVK"
FT   HELIX           140..152
FT                   /evidence="ECO:0007829|PDB:3TVK"
FT   STRAND          157..166
FT                   /evidence="ECO:0007829|PDB:3TVK"
FT   HELIX           169..176
FT                   /evidence="ECO:0007829|PDB:3TVK"
FT   HELIX           178..194
FT                   /evidence="ECO:0007829|PDB:3TVK"
FT   STRAND          202..204
FT                   /evidence="ECO:0007829|PDB:3TVK"
FT   STRAND          206..218
FT                   /evidence="ECO:0007829|PDB:3TVK"
FT   HELIX           219..235
FT                   /evidence="ECO:0007829|PDB:3TVK"
FT   STRAND          238..240
FT                   /evidence="ECO:0007829|PDB:3TVK"
FT   STRAND          243..245
FT                   /evidence="ECO:0007829|PDB:3TVK"
FT   STRAND          249..256
FT                   /evidence="ECO:0007829|PDB:3TVK"
FT   HELIX           262..278
FT                   /evidence="ECO:0007829|PDB:3TVK"
FT   STRAND          281..287
FT                   /evidence="ECO:0007829|PDB:3TVK"
FT   STRAND          293..295
FT                   /evidence="ECO:0007829|PDB:3TVK"
SQ   SEQUENCE   296 AA;  33863 MW;  7B6884E6B8A6D8D8 CRC64;
     MIKKTTEIDA ILLNLNKAID AHYQWLVSMF HSVVARDASK PEITDNHSYG LCQFGRWIDH
     LGPLDNDELP YVRLMDSAHQ HMHNCGRELM LAIVENHWQD AHFDAFQEGL LSFTAALTDY
     KIYLLTIRSN MDVLTGLPGR RVLDESFDHQ LRNAEPLNLY LMLLDIDRFK LVNDTYGHLI
     GDVVLRTLAT YLASWTRDYE TVYRYGGEEF IIIVKAANDE EACRAGVRIC QLVDNHAITH
     SEGHINITVT AGVSRAFPEE PLDVVIGRAD RAMYEGKQTG RNRCMFIDEQ NVINRV
//