CNPD3_MYCTU
ID CNPD3_MYCTU Reviewed; 318 AA.
AC P9WP65; L0T7J7; O06629; Q7D993;
DT 16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2014, sequence version 1.
DT 03-AUG-2022, entry version 46.
DE RecName: Full=cAMP/cGMP dual specificity phosphodiesterase Rv0805 {ECO:0000305};
DE EC=3.1.4.16 {ECO:0000269|PubMed:18757371, ECO:0000269|PubMed:19801656, ECO:0000269|PubMed:24970891};
DE EC=3.1.4.17 {ECO:0000269|PubMed:16313172, ECO:0000269|PubMed:18757371, ECO:0000269|PubMed:19801656};
DE AltName: Full=2',3'-cyclic-nucleotide phosphodiesterase {ECO:0000303|PubMed:18757371};
DE AltName: Full=3',5'-cyclic-nucleotide phosphodiesterase {ECO:0000303|PubMed:16313172};
DE AltName: Full=Cyclic nucleotide phosphodiesterase {ECO:0000303|PubMed:16313172};
GN OrderedLocusNames=Rv0805;
OS Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv).
OC Bacteria; Actinobacteria; Corynebacteriales; Mycobacteriaceae;
OC Mycobacterium; Mycobacterium tuberculosis complex.
OX NCBI_TaxID=83332;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=9634230; DOI=10.1038/31159;
RA Cole S.T., Brosch R., Parkhill J., Garnier T., Churcher C.M., Harris D.E.,
RA Gordon S.V., Eiglmeier K., Gas S., Barry C.E. III, Tekaia F., Badcock K.,
RA Basham D., Brown D., Chillingworth T., Connor R., Davies R.M., Devlin K.,
RA Feltwell T., Gentles S., Hamlin N., Holroyd S., Hornsby T., Jagels K.,
RA Krogh A., McLean J., Moule S., Murphy L.D., Oliver S., Osborne J.,
RA Quail M.A., Rajandream M.A., Rogers J., Rutter S., Seeger K., Skelton S.,
RA Squares S., Squares R., Sulston J.E., Taylor K., Whitehead S.,
RA Barrell B.G.;
RT "Deciphering the biology of Mycobacterium tuberculosis from the complete
RT genome sequence.";
RL Nature 393:537-544(1998).
RN [2]
RP FUNCTION, CATALYTIC ACTIVITY, COFACTOR, ACTIVITY REGULATION,
RP BIOPHYSICOCHEMICAL PROPERTIES, SUBUNIT, MUTAGENESIS OF ASP-21; HIS-23;
RP ASP-66; ASN-97; HIS-169 AND HIS-207, AND HOMOLOGY MODELING.
RX PubMed=16313172; DOI=10.1021/bi0512391;
RA Shenoy A.R., Sreenath N., Podobnik M., Kovacevic M., Visweswariah S.S.;
RT "The Rv0805 gene from Mycobacterium tuberculosis encodes a 3',5'-cyclic
RT nucleotide phosphodiesterase: biochemical and mutational analysis.";
RL Biochemistry 44:15695-15704(2005).
RN [3]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND
RP MUTAGENESIS OF HIS-98.
RX PubMed=18757371; DOI=10.1074/jbc.m805064200;
RA Keppetipola N., Shuman S.;
RT "A phosphate-binding histidine of binuclear metallophosphodiesterase
RT enzymes is a determinant of 2',3'-cyclic nucleotide phosphodiesterase
RT activity.";
RL J. Biol. Chem. 283:30942-30949(2008).
RN [4]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=21969609; DOI=10.1074/mcp.m111.011627;
RA Kelkar D.S., Kumar D., Kumar P., Balakrishnan L., Muthusamy B., Yadav A.K.,
RA Shrivastava P., Marimuthu A., Anand S., Sundaram H., Kingsbury R.,
RA Harsha H.C., Nair B., Prasad T.S., Chauhan D.S., Katoch K., Katoch V.M.,
RA Kumar P., Chaerkady R., Ramachandran S., Dash D., Pandey A.;
RT "Proteogenomic analysis of Mycobacterium tuberculosis by high resolution
RT mass spectrometry.";
RL Mol. Cell. Proteomics 10:M111.011627-M111.011627(2011).
RN [5]
RP OVEREXPRESSION.
RC STRAIN=H37Rv;
RX PubMed=23835087; DOI=10.1016/j.tube.2013.05.004;
RA Matange N., Hunt D.M., Buxton R.S., Visweswariah S.S.;
RT "Overexpression of the Rv0805 phosphodiesterase elicits a cAMP-independent
RT transcriptional response.";
RL Tuberculosis 93:492-500(2013).
RN [6]
RP CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, SUBCELLULAR LOCATION,
RP DOMAIN, AND MUTAGENESIS OF ASP-21; HIS-23; ASP-66; ASN-97; HIS-98; HIS-169;
RP HIS-207 AND HIS-209.
RX PubMed=24970891; DOI=10.1074/jbc.m114.578328;
RA Matange N., Podobnik M., Visweswariah S.S.;
RT "The non-catalytic 'cap domain' of a mycobacterial metallophosphoesterase
RT regulates its expression and localization in the cell.";
RL J. Biol. Chem. 289:22470-22481(2014).
RN [7]
RP NOMENCLATURE, AND REVIEW.
RX PubMed=26424768; DOI=10.1093/femsle/fnv183;
RA Matange N.;
RT "Revisiting bacterial cyclic nucleotide phosphodiesterases: cyclic AMP
RT hydrolysis and beyond.";
RL FEMS Microbiol. Lett. 362:0-0(2015).
RN [8]
RP COFACTOR, AND ACTIVITY REGULATION.
RX PubMed=26662456; DOI=10.1002/chem.201504001;
RA Pedroso M.M., Larrabee J.A., Ely F., Gwee S.E., Mitic N., Ollis D.L.,
RA Gahan L.R., Schenk G.;
RT "Ca(II) binding regulates and dominates the reactivity of a transition-
RT metal-ion-dependent diesterase from Mycobacterium tuberculosis.";
RL Chemistry 22:999-1009(2016).
RN [9]
RP PHOSPHORYLATION AT THR-309, SUBCELLULAR LOCATION, AND MUTAGENESIS OF
RP THR-309.
RX PubMed=26904001; DOI=10.3389/fmicb.2016.00123;
RA Malhotra N., Chakraborti P.K.;
RT "Eukaryotic-type Ser/Thr protein kinase mediated phosphorylation of
RT mycobacterial phosphodiesterase affects its localization to the cell
RT wall.";
RL Front. Microbiol. 7:123-123(2016).
RN [10] {ECO:0007744|PDB:2HY1, ECO:0007744|PDB:2HYO, ECO:0007744|PDB:2HYP}
RP X-RAY CRYSTALLOGRAPHY (1.93 ANGSTROMS) OF 3-278 OF WILD-TYPE; MUTANT ALA-66
RP AND MUTANT ALA-97 IN COMPLEXES WITH IRON AND MANGANESE, COFACTOR, SUBUNIT,
RP AND MUTAGENESIS OF HIS-140.
RX PubMed=17059828; DOI=10.1016/j.jmb.2006.10.005;
RA Shenoy A.R., Capuder M., Draskovic P., Lamba D., Visweswariah S.S.,
RA Podobnik M.;
RT "Structural and biochemical analysis of the Rv0805 cyclic nucleotide
RT phosphodiesterase from Mycobacterium tuberculosis.";
RL J. Mol. Biol. 365:211-225(2007).
RN [11] {ECO:0007744|PDB:3IB7, ECO:0007744|PDB:3IB8}
RP X-RAY CRYSTALLOGRAPHY (1.60 ANGSTROMS) OF 2-318 IN COMPLEX WITH IRON;
RP MANGANESE AND AMP, FUNCTION, CATALYTIC ACTIVITY, COFACTOR,
RP BIOPHYSICOCHEMICAL PROPERTIES, SUBUNIT, SUBCELLULAR LOCATION, DOMAIN, AND
RP MUTAGENESIS OF ASN-97; HIS-98; HIS-140; HIS-209 AND TYR-229.
RX PubMed=19801656; DOI=10.1074/jbc.m109.049635;
RA Podobnik M., Tyagi R., Matange N., Dermol U., Gupta A.K., Mattoo R.,
RA Seshadri K., Visweswariah S.S.;
RT "A mycobacterial cyclic AMP phosphodiesterase that moonlights as a modifier
RT of cell wall permeability.";
RL J. Biol. Chem. 284:32846-32857(2009).
CC -!- FUNCTION: Cyclic nucleotide phosphodiesterase with a dual-specificity
CC for the second messengers cAMP and cGMP (PubMed:16313172,
CC PubMed:18757371). Can use 2',3'-cAMP, 2',3'-cGMP, 3',5'-cAMP, 3',5'-
CC cGMP and 3',5'-cUMP (PubMed:16313172, PubMed:18757371,
CC PubMed:19801656). Hydrolysis of 2',3'-cAMP produces a mixture of 3'-AMP
CC (major product) and 2'-AMP (minor product) (PubMed:18757371). In vitro,
CC is 150-fold more active in hydrolyzing 2',3'-cAMP than 3',5'-cAMP
CC (PubMed:18757371). Can also hydrolyze the model substrates p-
CC nitrophenyl phosphate (pNPP), bis-(p-nitrophenyl phosphate) (bis(pNPP))
CC and p-nitrophenyl phenylphosphonate (pNPPP) (PubMed:16313172,
CC PubMed:18757371, PubMed:19801656). Plays an important regulatory role
CC in modulating the intracellular concentration of cAMP, thereby
CC influencing cAMP-dependent processes (PubMed:16313172). May play a role
CC in pathogenicity, not only by hydrolyzing cAMP, but also by altering
CC properties of the cell wall (PubMed:19801656).
CC {ECO:0000269|PubMed:16313172, ECO:0000269|PubMed:18757371,
CC ECO:0000269|PubMed:19801656}.
CC -!- FUNCTION: Overexpression elicits a transcriptional response that is
CC independent of the phosphodiesterase activity. It does not alter the
CC levels of cAMP-CRP regulated genes, even though cAMP levels are reduced
CC in cells. {ECO:0000269|PubMed:23835087}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a nucleoside 2',3'-cyclic phosphate + H2O = a nucleoside 3'-
CC phosphate + H(+); Xref=Rhea:RHEA:19621, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:66949, ChEBI:CHEBI:66954; EC=3.1.4.16;
CC Evidence={ECO:0000269|PubMed:18757371, ECO:0000269|PubMed:19801656,
CC ECO:0000269|PubMed:24970891};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2',3'-cyclophospho-AMP + H2O = 3'-AMP + H(+);
CC Xref=Rhea:RHEA:27886, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:60879, ChEBI:CHEBI:60880; EC=3.1.4.16;
CC Evidence={ECO:0000269|PubMed:18757371, ECO:0000269|PubMed:19801656,
CC ECO:0000269|PubMed:24970891};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2',3'-cyclophospho-AMP + H2O = adenosine 2'-phosphate + H(+);
CC Xref=Rhea:RHEA:37191, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:60879, ChEBI:CHEBI:77740;
CC Evidence={ECO:0000269|PubMed:18757371};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2',3'-cyclophospho-GMP + H2O = 3'-GMP + H(+);
CC Xref=Rhea:RHEA:27858, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:60732, ChEBI:CHEBI:60837; EC=3.1.4.16;
CC Evidence={ECO:0000269|PubMed:18757371};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a nucleoside 3',5'-cyclic phosphate + H2O = a nucleoside 5'-
CC phosphate + H(+); Xref=Rhea:RHEA:14653, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57867, ChEBI:CHEBI:58464; EC=3.1.4.17;
CC Evidence={ECO:0000269|PubMed:16313172, ECO:0000269|PubMed:18757371,
CC ECO:0000269|PubMed:19801656};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3',5'-cyclic AMP + H2O = AMP + H(+); Xref=Rhea:RHEA:25277,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:58165,
CC ChEBI:CHEBI:456215; Evidence={ECO:0000269|PubMed:16313172,
CC ECO:0000269|PubMed:18757371, ECO:0000269|PubMed:19801656};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3',5'-cyclic GMP + H2O = GMP + H(+); Xref=Rhea:RHEA:16957,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:57746,
CC ChEBI:CHEBI:58115; Evidence={ECO:0000269|PubMed:16313172,
CC ECO:0000269|PubMed:18757371};
CC -!- COFACTOR:
CC Name=Fe(3+); Xref=ChEBI:CHEBI:29034;
CC Evidence={ECO:0000269|PubMed:16313172, ECO:0000269|PubMed:17059828,
CC ECO:0000269|PubMed:19801656, ECO:0000269|PubMed:26662456};
CC Note=Binds 1 Fe(3+) ion per subunit. {ECO:0000269|PubMed:17059828,
CC ECO:0000269|PubMed:19801656};
CC -!- COFACTOR:
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000269|PubMed:16313172, ECO:0000269|PubMed:17059828,
CC ECO:0000269|PubMed:19801656, ECO:0000269|PubMed:26662456};
CC Note=Binds 1 Mn(2+) ion per subunit. {ECO:0000269|PubMed:17059828,
CC ECO:0000269|PubMed:19801656};
CC -!- ACTIVITY REGULATION: Ca(2+) acts as an activator of the enzymatic
CC activity and is able to promote the hydrolysis of substrates even in
CC the absence of transition-metal ions, thus providing an effective
CC strategy for the regulation of the enzymatic activity. Two Ca(2+) ions
CC bind at a site different from the dinuclear transition-metal-ion
CC binding site (PubMed:26662456). Activity is enhanced by magnesium or
CC manganese. Activity decreases in the presence of orthovanadate and
CC phosphotyrosine (PubMed:16313172). {ECO:0000269|PubMed:16313172,
CC ECO:0000269|PubMed:26662456}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=5.5 mM for 3',5'-cAMP {ECO:0000269|PubMed:19801656};
CC KM=1.6 mM for 2',3'-cAMP {ECO:0000269|PubMed:18757371};
CC KM=0.537 mM for 2',3'-cAMP {ECO:0000269|PubMed:24970891};
CC KM=1 mM for 2',3'-cAMP {ECO:0000269|PubMed:19801656};
CC KM=1.7 mM for pNPP {ECO:0000269|PubMed:18757371};
CC KM=0.9 mM for bis(pNPP) {ECO:0000269|PubMed:18757371,
CC ECO:0000269|PubMed:19801656};
CC KM=0.295 mM for bis(pNPP) {ECO:0000269|PubMed:24970891};
CC KM=0.9 mM for pNPPP {ECO:0000269|PubMed:19801656};
CC Vmax=1.1 umol/min/mg enzyme with 3',5'-cAMP as substrate
CC {ECO:0000269|PubMed:19801656};
CC Vmax=14.7 umol/min/mg enzyme with 2',3'-cAMP as substrate
CC {ECO:0000269|PubMed:19801656};
CC Vmax=6.9 umol/min/mg enzyme with 2',3'-cAMP as substrate
CC {ECO:0000269|PubMed:24970891};
CC Vmax=0.017 umol/min/mg enzyme with pNPP as substrate
CC {ECO:0000269|PubMed:19801656};
CC Vmax=74 umol/min/mg enzyme with bis(pNPP) as substrate
CC {ECO:0000269|PubMed:19801656};
CC Vmax=34.8 umol/min/mg enzyme with bis(pNPP) as substrate
CC {ECO:0000269|PubMed:24970891};
CC Vmax=112.7 umol/min/mg enzyme with pNPPP as substrate
CC {ECO:0000269|PubMed:19801656};
CC Note=kcat is 2.8 sec(-1) with 2',3'-cAMP as substrate. kcat is 0.55
CC sec(-1) with pNPP as substrate. kcat is 12.4 sec(-1) with bis(pNPP)
CC as substrate. {ECO:0000269|PubMed:18757371};
CC pH dependence:
CC Optimum pH is 8.5-9.5. {ECO:0000269|PubMed:16313172};
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:16313172,
CC ECO:0000269|PubMed:17059828, ECO:0000269|PubMed:19801656}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:19801656,
CC ECO:0000269|PubMed:24970891}. Cell membrane
CC {ECO:0000269|PubMed:19801656, ECO:0000269|PubMed:24970891}. Secreted,
CC cell wall {ECO:0000269|PubMed:19801656, ECO:0000269|PubMed:24970891,
CC ECO:0000269|PubMed:26904001}. Cell envelope
CC {ECO:0000269|PubMed:24970891}. Note=The C-terminal extension (CTE) is
CC necessary for the localization to the cell wall and cell envelope
CC (PubMed:19801656, PubMed:24970891). Phosphorylation at Thr-309 promotes
CC cell wall localization (PubMed:26904001). {ECO:0000269|PubMed:19801656,
CC ECO:0000269|PubMed:24970891, ECO:0000269|PubMed:26904001}.
CC -!- DOMAIN: The C-terminal extension (CTE) is used to better adjust the
CC substrates into the active sites and mediates in vivo subcellular
CC localization of the protein (PubMed:19801656, PubMed:24970891). It also
CC modulates expression levels of Rv0805 in mycobacteria
CC (PubMed:24970891). {ECO:0000269|PubMed:19801656,
CC ECO:0000269|PubMed:24970891}.
CC -!- PTM: Phosphorylated on Thr-309 by the eukaryotic-type serine/threonine-
CC protein kinases PknA, PknB and PknL. Phosphorylation does not affect
CC the enzymatic activity, but it renders negative charge to the protein,
CC promoting its localization on cell wall. {ECO:0000269|PubMed:26904001}.
CC -!- SIMILARITY: Belongs to the cyclic nucleotide phosphodiesterase class-
CC III family. {ECO:0000305|PubMed:26424768}.
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DR EMBL; AL123456; CCP43553.1; -; Genomic_DNA.
DR PIR; F70536; F70536.
DR RefSeq; NP_215320.1; NC_000962.3.
DR RefSeq; WP_003404120.1; NZ_NVQJ01000064.1.
DR PDB; 2HY1; X-ray; 1.93 A; A=3-278.
DR PDB; 2HYO; X-ray; 2.25 A; A=3-278.
DR PDB; 2HYP; X-ray; 2.05 A; A=3-278.
DR PDB; 3IB7; X-ray; 1.60 A; A=2-318.
DR PDB; 3IB8; X-ray; 1.80 A; A=2-318.
DR PDBsum; 2HY1; -.
DR PDBsum; 2HYO; -.
DR PDBsum; 2HYP; -.
DR PDBsum; 3IB7; -.
DR PDBsum; 3IB8; -.
DR AlphaFoldDB; P9WP65; -.
DR SMR; P9WP65; -.
DR STRING; 83332.Rv0805; -.
DR PaxDb; P9WP65; -.
DR DNASU; 885326; -.
DR GeneID; 885326; -.
DR KEGG; mtu:Rv0805; -.
DR TubercuList; Rv0805; -.
DR eggNOG; COG1409; Bacteria.
DR OMA; CAWLDQH; -.
DR PhylomeDB; P9WP65; -.
DR BRENDA; 3.1.4.17; 3445.
DR PHI-base; PHI:4238; -.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0031975; C:envelope; IEA:UniProtKB-SubCell.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-KW.
DR GO; GO:0009274; C:peptidoglycan-based cell wall; IDA:MTBBASE.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0008663; F:2',3'-cyclic-nucleotide 2'-phosphodiesterase activity; IDA:MTBBASE.
DR GO; GO:0004115; F:3',5'-cyclic-AMP phosphodiesterase activity; IDA:MTBBASE.
DR GO; GO:0047555; F:3',5'-cyclic-GMP phosphodiesterase activity; IEA:RHEA.
DR GO; GO:0008199; F:ferric iron binding; IDA:MTBBASE.
DR GO; GO:0005506; F:iron ion binding; IDA:MTBBASE.
DR GO; GO:0030145; F:manganese ion binding; IDA:MTBBASE.
DR GO; GO:0000166; F:nucleotide binding; IEA:UniProtKB-KW.
DR GO; GO:0042301; F:phosphate ion binding; IDA:MTBBASE.
DR GO; GO:0042545; P:cell wall modification; IDA:MTBBASE.
DR CDD; cd07402; MPP_GpdQ; 1.
DR Gene3D; 3.60.21.10; -; 1.
DR InterPro; IPR004843; Calcineurin-like_PHP_ApaH.
DR InterPro; IPR026575; GpdQ/CpdA-like.
DR InterPro; IPR029052; Metallo-depent_PP-like.
DR Pfam; PF00149; Metallophos; 1.
DR SUPFAM; SSF56300; SSF56300; 1.
PE 1: Evidence at protein level;
KW 3D-structure; cAMP; Cell membrane; Cell wall; cGMP; Cytoplasm; Hydrolase;
KW Iron; Manganese; Membrane; Metal-binding; Nucleotide-binding;
KW Phosphoprotein; Reference proteome; Secreted.
FT CHAIN 1..318
FT /note="cAMP/cGMP dual specificity phosphodiesterase Rv0805"
FT /id="PRO_0000413370"
FT REGION 278..318
FT /note="C-terminal extension"
FT /evidence="ECO:0000305|PubMed:24970891"
FT BINDING 21
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000269|PubMed:17059828,
FT ECO:0000269|PubMed:19801656"
FT BINDING 23
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /evidence="ECO:0000269|PubMed:19801656,
FT ECO:0007744|PDB:3IB8"
FT BINDING 23
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000269|PubMed:17059828,
FT ECO:0000269|PubMed:19801656"
FT BINDING 63
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /evidence="ECO:0000269|PubMed:19801656,
FT ECO:0007744|PDB:3IB8"
FT BINDING 63
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000269|PubMed:17059828,
FT ECO:0000269|PubMed:19801656"
FT BINDING 63
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /evidence="ECO:0000269|PubMed:17059828,
FT ECO:0000269|PubMed:19801656"
FT BINDING 97..98
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /evidence="ECO:0000269|PubMed:19801656,
FT ECO:0007744|PDB:3IB8"
FT BINDING 97
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /evidence="ECO:0000269|PubMed:17059828,
FT ECO:0000269|PubMed:19801656"
FT BINDING 169
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /evidence="ECO:0000269|PubMed:17059828,
FT ECO:0000269|PubMed:19801656"
FT BINDING 207
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /evidence="ECO:0000269|PubMed:17059828,
FT ECO:0000269|PubMed:19801656"
FT BINDING 209
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /evidence="ECO:0000269|PubMed:19801656,
FT ECO:0007744|PDB:3IB8"
FT BINDING 209
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000269|PubMed:17059828,
FT ECO:0000269|PubMed:19801656"
FT MOD_RES 309
FT /note="Phosphothreonine"
FT /evidence="ECO:0000269|PubMed:26904001"
FT MUTAGEN 21
FT /note="D->A: 90% decrease in bis(pNPP) hydrolysis. Does not
FT affect cAMP hydrolysis. Strong decrease in interaction with
FT the cell wall."
FT /evidence="ECO:0000269|PubMed:16313172,
FT ECO:0000269|PubMed:24970891"
FT MUTAGEN 23
FT /note="H->A: 50% decrease in bis(pNPP) hydrolysis. Does not
FT affect cAMP hydrolysis. Strong decrease in interaction with
FT the cell wall."
FT /evidence="ECO:0000269|PubMed:16313172,
FT ECO:0000269|PubMed:24970891"
FT MUTAGEN 66
FT /note="D->A: 25% decrease in bis(pNPP) hydrolysis. 70%
FT decrease in cAMP hydrolysis. Decreases interaction with the
FT cell wall."
FT /evidence="ECO:0000269|PubMed:16313172,
FT ECO:0000269|PubMed:24970891"
FT MUTAGEN 97
FT /note="N->A: Loss of bis(pNPP) and 3',5'-cAMP hydrolysis.
FT Strong decrease in 2',3'-cAMP hydrolysis. Slight decrease
FT in interaction with the cell wall."
FT /evidence="ECO:0000269|PubMed:16313172,
FT ECO:0000269|PubMed:19801656, ECO:0000269|PubMed:24970891"
FT MUTAGEN 98
FT /note="H->A: 40% decrease in bis(pNPP) hydrolysis. Strong
FT decrease in 3',5'-cAMP and 2',3'-cAMP hydrolysis. Abolishes
FT pNPP hydrolysis. Decreases interaction with the cell wall."
FT /evidence="ECO:0000269|PubMed:18757371,
FT ECO:0000269|PubMed:19801656, ECO:0000269|PubMed:24970891"
FT MUTAGEN 98
FT /note="H->N: 2-fold increase in bis(pNPP) hydrolysis. 4-
FT fold decrease in pNPP hydrolysis. 5-fold decrease in 2',3'-
FT cAMP hydrolysis."
FT /evidence="ECO:0000269|PubMed:18757371"
FT MUTAGEN 140
FT /note="H->A: No change in activity."
FT /evidence="ECO:0000269|PubMed:17059828,
FT ECO:0000269|PubMed:19801656"
FT MUTAGEN 169
FT /note="H->A: 50% decrease in bis(pNPP) hydrolysis. Does not
FT affect cAMP hydrolysis. Decreases interaction with the cell
FT wall."
FT /evidence="ECO:0000269|PubMed:16313172,
FT ECO:0000269|PubMed:24970891"
FT MUTAGEN 207
FT /note="H->A: 75% decrease in bis(pNPP) hydrolysis. Does not
FT affect cAMP hydrolysis. Decreases catalytic efficiency and
FT shows lower affinity for both linear and cyclic substrates.
FT Almost completely abrogates interaction with the cell wall
FT in vitro."
FT /evidence="ECO:0000269|PubMed:16313172,
FT ECO:0000269|PubMed:24970891"
FT MUTAGEN 209
FT /note="H->A: 80% decrease in hydrolysis of 3',5'-cAMP and
FT bis(pNPP). 40% decrease in 2',3'-cAMP hydrolysis. Strong
FT decrease in interaction with the cell wall."
FT /evidence="ECO:0000269|PubMed:19801656,
FT ECO:0000269|PubMed:24970891"
FT MUTAGEN 229
FT /note="Y->A: 40% decrease in bis(pNPP) hydrolysis. 80%
FT decrease in 3',5'-cAMP and 2',3'-cAMP hydrolysis."
FT /evidence="ECO:0000269|PubMed:19801656"
FT MUTAGEN 309
FT /note="T->A: 8-fold decrease in phosphorylation. Affects
FT localization to the cell wall."
FT /evidence="ECO:0000269|PubMed:26904001"
FT MUTAGEN 309
FT /note="T->D,E: Does not affect localization to the cell
FT wall."
FT /evidence="ECO:0000269|PubMed:26904001"
FT STRAND 13..19
FT /evidence="ECO:0007829|PDB:3IB7"
FT STRAND 26..28
FT /evidence="ECO:0007829|PDB:3IB7"
FT TURN 32..34
FT /evidence="ECO:0007829|PDB:3IB7"
FT HELIX 37..51
FT /evidence="ECO:0007829|PDB:3IB7"
FT STRAND 56..60
FT /evidence="ECO:0007829|PDB:3IB7"
FT STRAND 65..67
FT /evidence="ECO:0007829|PDB:2HY1"
FT HELIX 70..87
FT /evidence="ECO:0007829|PDB:3IB7"
FT STRAND 90..93
FT /evidence="ECO:0007829|PDB:3IB7"
FT HELIX 101..109
FT /evidence="ECO:0007829|PDB:3IB7"
FT STRAND 120..124
FT /evidence="ECO:0007829|PDB:3IB7"
FT STRAND 127..131
FT /evidence="ECO:0007829|PDB:3IB7"
FT STRAND 140..142
FT /evidence="ECO:0007829|PDB:2HY1"
FT HELIX 146..155
FT /evidence="ECO:0007829|PDB:3IB7"
FT STRAND 164..167
FT /evidence="ECO:0007829|PDB:3IB7"
FT HELIX 178..183
FT /evidence="ECO:0007829|PDB:3IB7"
FT STRAND 184..186
FT /evidence="ECO:0007829|PDB:3IB7"
FT HELIX 188..195
FT /evidence="ECO:0007829|PDB:3IB7"
FT STRAND 198..205
FT /evidence="ECO:0007829|PDB:3IB7"
FT STRAND 207..210
FT /evidence="ECO:0007829|PDB:3IB7"
FT STRAND 212..216
FT /evidence="ECO:0007829|PDB:3IB7"
FT STRAND 219..223
FT /evidence="ECO:0007829|PDB:3IB7"
FT STRAND 242..244
FT /evidence="ECO:0007829|PDB:3IB7"
FT STRAND 248..254
FT /evidence="ECO:0007829|PDB:3IB7"
FT STRAND 259..265
FT /evidence="ECO:0007829|PDB:3IB7"
FT HELIX 278..287
FT /evidence="ECO:0007829|PDB:3IB7"
SQ SEQUENCE 318 AA; 34233 MW; 7C1B683C5E375B3F CRC64;
MHRLRAAEHP RPDYVLLHIS DTHLIGGDRR LYGAVDADDR LGELLEQLNQ SGLRPDAIVF
TGDLADKGEP AAYRKLRGLV EPFAAQLGAE LVWVMGNHDD RAELRKFLLD EAPSMAPLDR
VCMIDGLRII VLDTSVPGHH HGEIRASQLG WLAEELATPA PDGTILALHH PPIPSVLDMA
VTVELRDQAA LGRVLRGTDV RAILAGHLHY STNATFVGIP VSVASATCYT QDLTVAAGGT
RGRDGAQGCN LVHVYPDTVV HSVIPLGGGE TVGTFVSPGQ ARRKIAESGI FIEPSRRDSL
FKHPPMVLTS SAPRSPVD
