O06629 (CPDA_MYCTU) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
3',5'-cyclic adenosine monophosphate phosphodiesterase CpdA
Short name=3',5'-cyclic AMP phosphodiesterase
Short name=cAMP phosphodiesterase
EC=3.1.4.17

Gene names

Name:	cpdA
Synonyms:	icc
Ordered Locus Names:	Rv0805, MT0825

Organism

Mycobacterium tuberculosis [Reference proteome] [HAMAP]

Taxonomic identifier

1773 [NCBI]

Taxonomic lineage

cellular organisms › Bacteria › Actinobacteria › Actinobacteria › Actinobacteridae › Actinomycetales › Corynebacterineae › Mycobacteriaceae › Mycobacterium › Mycobacterium tuberculosis complex

Protein attributes

Sequence length	318 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Hydrolyzes cAMP to 5'-AMP. Plays an important regulatory role in modulating the intracellular concentration of cAMP, thereby influencing cAMP-dependent processes. Can also hydrolyze cGMP, p-nitrophenyl phosphate (pNPP), bis-(p-nitrophenyl phosphate) (bis(pNPP)), p-nitrophenyl phenylphosphonate (pNPPP) and 2',3'-cAMP. May play a role in pathogenicity, not only by hydrolyzing cAMP, but also by altering properties of the cell wall. Ref.3 Ref.5
Catalytic activity	Adenosine 3',5'-cyclic phosphate + H2O = adenosine 5'-phosphate. Ref.3 Ref.5
Cofactor	Binds 1 Fe3+ ion per subunit. Binds 1 Mn2+ ion per subunit.
Enzyme regulation	Enhanced by magnesium or manganese. Activity decreases in the presence of orthovanadate and phosphotyrosine. Ref.3
Subunit structure	Homodimer. Ref.3 Ref.4 Ref.5
Subcellular location	Cytoplasm. Cell membrane. Secreted › cell wall. Note: Localization to the cell membrane and cell wall could be due to a specialized secretion system operative in mycobacteria. HAMAP-Rule MF_00905
Domain	The C-terminal domain is used to better adjust the substrates into the active sites and to facilitate subcellular localization of the protein. Ref.5
Sequence similarities	Belongs to the cAMP phosphodiesterase class-III family.
Biophysicochemical properties	Kinetic parameters: KM=5.5 mM for 3',5'-cAMP Ref.3 Ref.5 KM=0.9 mM for bis(pNPP) KM=0.9 mM for pNPPP KM=1 mM for 2',3'-cAMP Vmax=1.1 µmol/min/mg enzyme with 3',5'-cAMP as substrate Vmax=74 µmol/min/mg enzyme with bis(pNPP) as substrate Vmax=112.7 µmol/min/mg enzyme with pNPPP as substrate Vmax=14.7 µmol/min/mg enzyme with 2',3'-cAMP as substrate Vmax=0.017 µmol/min/mg enzyme with pNPP as substrate pH dependence: Optimum pH is 8.5-9.5.

Ontologies

Keywords
Cellular component	Cell membrane Cell wall Cytoplasm Membrane Secreted
Ligand	Iron Manganese Metal-binding Nucleotide-binding cAMP
Molecular function	Hydrolase
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cAMP catabolic process Inferred from direct assay PubMed 19516256Ref.5. Source: MTBBASE cell wall modification Inferred from direct assay Ref.5. Source: MTBBASE pathogenesis Inferred from mutant phenotype PubMed 18956986. Source: MTBBASE
Cellular_component	cell wall Inferred from direct assay Ref.5. Source: MTBBASE cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell extracellular region Inferred from electronic annotation. Source: UniProtKB-KW plasma membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	2',3'-cyclic-nucleotide 2'-phosphodiesterase activity Inferred from direct assay Ref.5. Source: MTBBASE 3',5'-cyclic-AMP phosphodiesterase activity Inferred from direct assay Ref.3PubMed 18757371Ref.5. Source: MTBBASE 4-nitrophenylphosphatase activity Inferred from direct assay Ref.5. Source: MTBBASE ferric iron binding Inferred from direct assay Ref.4. Source: MTBBASE manganese ion binding Inferred from direct assay Ref.3Ref.4Ref.5. Source: MTBBASE nucleotide binding Inferred from electronic annotation. Source: HAMAP phosphate ion binding Inferred from direct assay Ref.4. Source: MTBBASE
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 318

318

3',5'-cyclic adenosine monophosphate phosphodiesterase CpdA HAMAP-Rule MF_00905

PRO_0000413370

Regions

Nucleotide binding

97 – 98

2

cAMP HAMAP-Rule MF_00905

Sites

Metal binding

21

1

Iron

Metal binding

23

1

Iron

Metal binding

63

1

Iron

Metal binding

63

1

Manganese

Metal binding

97

1

Manganese

Metal binding

169

1

Manganese

Metal binding

207

1

Manganese

Metal binding

209

1

Iron

Binding site

23

1

cAMP

Binding site

63

1

cAMP

Binding site

209

1

cAMP

Experimental info

Mutagenesis

21

1

D → A: 90% decrease in bis(pNPP) hydrolysis. Does not affect cAMP hydrolysis. Ref.3

Mutagenesis

23

1

H → A: 50% decrease in bis(pNPP) hydrolysis. Does not affect cAMP hydrolysis. Ref.3

Mutagenesis

66

1

D → A: 25% decrease in bis(pNPP) hydrolysis. 70% decrease in cAMP hydrolysis. Ref.3

Mutagenesis

97

1

N → A: Loss of bis(pNPP) and 3',5'-cAMP hydrolysis. Strong decrease in 2',3'-cAMP hydrolysis. Ref.3 Ref.5

Mutagenesis

98

1

H → A: 40% decrease in bis(pNPP) hydrolysis. Strong decrease in 3',5'-cAMP and 2',3'-cAMP hydrolysis. Ref.5

Mutagenesis

140

1

H → A: No change in activity. Ref.4 Ref.5

Mutagenesis

169

1

H → A: 50% decrease in bis(pNPP) hydrolysis. Does not affect cAMP hydrolysis. Ref.3

Mutagenesis

207

1

H → A: 75% decrease in bis(pNPP) hydrolysis. Does not affect cAMP hydrolysis. Ref.3

Mutagenesis

209

1

H → A: 80% decrease in hydrolysis of 3',5'-cAMP and bis(pNPP). 40% decrease in 2',3'-cAMP hydrolysis. Ref.5

Mutagenesis

229

1

Y → A: 40% decrease in bis(pNPP) hydrolysis. 80% decrease in 3',5'-cAMP and 2',3'-cAMP hydrolysis. Ref.5

Secondary structure

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318

Helix Strand Turn

Details...

Beta strand

13 – 19

7

Beta strand

26 – 28

3

Turn

32 – 34

3

Helix

37 – 51

15

Beta strand

56 – 60

5

Beta strand

65 – 67

3

Helix

70 – 87

18

Beta strand

90 – 93

4

Helix

101 – 109

9

Beta strand

120 – 124

5

Beta strand

127 – 131

5

Beta strand

140 – 142

3

Helix

146 – 155

10

Beta strand

164 – 167

4

Helix

178 – 183

6

Beta strand

184 – 186

3

Helix

188 – 195

8

Beta strand

198 – 205

8

Beta strand

207 – 210

4

Beta strand

212 – 216

5

Beta strand

219 – 223

5

Beta strand

242 – 244

3

Beta strand

248 – 254

7

Beta strand

259 – 265

7

Helix

278 – 287

10

Sequences

	Sequence		Length	Mass (Da)
	O06629 [UniParc]. Last modified July 1, 1997. Version 1. Checksum: 7C1B683C5E375B3F	FASTA	318	34,233
	10 20 30 40 50 60 MHRLRAAEHP RPDYVLLHIS DTHLIGGDRR LYGAVDADDR LGELLEQLNQ SGLRPDAIVF 70 80 90 100 110 120 TGDLADKGEP AAYRKLRGLV EPFAAQLGAE LVWVMGNHDD RAELRKFLLD EAPSMAPLDR 130 140 150 160 170 180 VCMIDGLRII VLDTSVPGHH HGEIRASQLG WLAEELATPA PDGTILALHH PPIPSVLDMA 190 200 210 220 230 240 VTVELRDQAA LGRVLRGTDV RAILAGHLHY STNATFVGIP VSVASATCYT QDLTVAAGGT 250 260 270 280 290 300 RGRDGAQGCN LVHVYPDTVV HSVIPLGGGE TVGTFVSPGQ ARRKIAESGI FIEPSRRDSL 310 FKHPPMVLTS SAPRSPVD

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequence." Cole S.T., Brosch R., Parkhill J., Garnier T., Churcher C.M., Harris D.E., Gordon S.V., Eiglmeier K., Gas S., Barry C.E. III, Tekaia F., Badcock K., Basham D., Brown D., Chillingworth T., Connor R., Davies R.M., Devlin K. , Feltwell T., Gentles S., Hamlin N., Holroyd S., Hornsby T., Jagels K., Krogh A., McLean J., Moule S., Murphy L.D., Oliver S., Osborne J., Quail M.A., Rajandream M.A., Rogers J., Rutter S., Seeger K., Skelton S., Squares S., Squares R., Sulston J.E., Taylor K., Whitehead S., Barrell B.G. Nature 393:537-544(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: ATCC 25618 / H37Rv.
[2]	"Whole-genome comparison of Mycobacterium tuberculosis clinical and laboratory strains." Fleischmann R.D., Alland D., Eisen J.A., Carpenter L., White O., Peterson J.D., DeBoy R.T., Dodson R.J., Gwinn M.L., Haft D.H., Hickey E.K., Kolonay J.F., Nelson W.C., Umayam L.A., Ermolaeva M.D., Salzberg S.L., Delcher A., Utterback T.R. , Weidman J.F., Khouri H.M., Gill J., Mikula A., Bishai W., Jacobs W.R. Jr., Venter J.C., Fraser C.M. J. Bacteriol. 184:5479-5490(2002) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: CDC 1551 / Oshkosh.
[3]	"The Rv0805 gene from Mycobacterium tuberculosis encodes a 3',5'-cyclic nucleotide phosphodiesterase: biochemical and mutational analysis." Shenoy A.R., Sreenath N., Podobnik M., Kovacevic M., Visweswariah S.S. Biochemistry 44:15695-15704(2005) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, CATALYTIC ACTIVITY, COFACTOR, ENZYME REGULATION, BIOPHYSICOCHEMICAL PROPERTIES, SUBUNIT, MUTAGENESIS OF ASP-21; HIS-23; ASP-66; ASN-97; HIS-169 AND HIS-207, HOMOLOGY MODELING.
[4]	"Structural and biochemical analysis of the Rv0805 cyclic nucleotide phosphodiesterase from Mycobacterium tuberculosis." Shenoy A.R., Capuder M., Draskovic P., Lamba D., Visweswariah S.S., Podobnik M. J. Mol. Biol. 365:211-225(2007) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.93 ANGSTROMS) OF 3-278 OF WILD-TYPE; MUTANT ALA-66 AND MUTANT ALA-97 IN COMPLEXES WITH IRON AND MANGANESE, COFACTOR, SUBUNIT, MUTAGENESIS OF HIS-140.
[5]	"A mycobacterial cyclic AMP phosphodiesterase that moonlights as a modifier of cell wall permeability." Podobnik M., Tyagi R., Matange N., Dermol U., Gupta A.K., Mattoo R., Seshadri K., Visweswariah S.S. J. Biol. Chem. 284:32846-32857(2009) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.60 ANGSTROMS) OF 2-318 IN COMPLEX WITH IRON; MANGANESE AND AMP, FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, SUBUNIT, SUCELLULAR LOCATION, DOMAIN, MUTAGENESIS OF ASN-97; HIS-98; HIS-140; HIS-209 AND TYR-229.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AE000516 Genomic DNA. Translation: AAK45067.1.
BX842574 Genomic DNA. Translation: CAB09106.1.
AL123456 Genomic DNA. Translation: CCP43553.1.

PIR

F70536.

RefSeq

NP_215320.1. NC_000962.3.
NP_335253.1. NC_002755.2.
YP_006514154.1. NC_018143.1.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2HY1	X-ray	1.93	A	3-278	[»]
2HYO	X-ray	2.25	A	3-278	[»]
2HYP	X-ray	2.05	A	3-278	[»]
3IB7	X-ray	1.60	A	2-318	[»]
3IB8	X-ray	1.80	A	2-318	[»]

ProteinModelPortal

O06629.

SMR

O06629. Positions 4-298.

ModBase

Search...

Protein-protein interaction databases

STRING

83332.Rv0805.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

EnsemblBacteria

AAK45067; AAK45067; MT0825.

GeneID

13318701.
885326.
926128.

KEGG

mtc:MT0825.
mtu:Rv0805.
mtv:RVBD_0805.

PATRIC

18123556. VBIMycTub22151_0906.

Organism-specific databases

TubercuList

Rv0805.

Phylogenomic databases

HOGENOM

HOG000238352.

OMA

HLHYSTT.

ProtClustDB

CLSK790749.

Family and domain databases

HAMAP

MF_00905. cAMP_phophodiest_CpdA.

InterPro

IPR026575. cAMP_Pdiest_CpdA.
IPR004843. Metallo_PEstase_dom.
[Graphical view]

Pfam

PF00149. Metallophos. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

O06629.

Entry information

Entry name

CPDA_MYCTU

Accession

Primary (citable) accession number: O06629
Secondary accession number(s): L0T7J7, Q7D993

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 19, 2011
Last sequence update:	July 1, 1997
Last modified:	May 1, 2013
This is version 80 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Prokaryotic Protein Annotation Program