Reviewed, UniProtKB/Swiss-Prot O52582 (CDR_STAA8)

Names and origin

Protein names

Recommended name:
    Coenzyme A disulfide reductase
      Short name=CoA-disulfide reductase
      Short name=CoADR
    EC=1.8.1.14

Gene names

Name:	cdr
Ordered Locus Names:	SAOUHSC_00908

Organism

Staphylococcus aureus (strain NCTC 8325) [Complete proteome] [HAMAP]

Taxonomic identifier

93061 [NCBI]

Taxonomic lineage

Bacteria › Firmicutes › Bacillales › Staphylococcus

Protein attributes

Sequence length	438 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Catalyzes specifically the NADPH-dependent reduction of coenzyme A disulfide. Is also active with other disulfide substrates containing at least one 4'-phosphopantethienyl moiety such as 4,4'-diphosphopantethine, but is not able to reduce oxidized glutathione, cystine, pantethine, or H2O2. HAMAP MF_01608
Catalytic activity	2 CoA + NAD(P)+ = CoA-disulfide + NAD(P)H. HAMAP MF_01608
Cofactor	Binds 1 FAD per subunit. HAMAP MF_01608
Subunit structure	Homodimer. Ref.5
Domain	Contains 2 FAD binding domains and a single NADPH binding domain. HAMAP MF_01608
Miscellaneous	Reduction of disulfides occurs by a thiol-disulfide exchange reaction, but involves only a single catalytic cysteine residue that forms a stable mixed disulfide with CoA during catalysis. HAMAP MF_01608
Sequence similarities	Belongs to the class-III pyridine nucleotide-disulfide oxidoreductase family.
biophysicochemical properties	Kinetic parameters: KM=2 µM for NADPH HAMAP MF_01608 KM=11 µM for CoA disulfide KM=140 µM for 3'-dephospho-CoA disulfide KM=80 µM for 4,4'-diphosphopantethine KM=1100 µM for CoA glutathione mixed disulfide pH dependence: Optimum pH is 7.0-8.0.
Mass spectrometry	Molecular mass is 49153 Da from positions 2 - 438. Determined by ESI. Ref.4

Ontologies

Keywords
Domain	Redox-active center
Ligand	FAD Flavoprotein NADP
Molecular function	Oxidoreductase
Technical term	3D-structure Complete proteome Direct protein sequencing
Gene Ontology (GO)
Biological process	cell redox homeostasis Inferred from electronic annotation. Source: InterPro oxidation reduction Inferred from electronic annotation. Source: UniProtKB-KW protein thiol-disulfide exchange Inferred from electronic annotation. Source: HAMAP
Cellular component	cytoplasm Inferred from electronic annotation. Source: InterPro
Molecular function	CoA-disulfide reductase activity Inferred from electronic annotation. Source: HAMAP FAD binding Inferred from electronic annotation. Source: HAMAP NADP or NADPH binding Inferred from electronic annotation. Source: HAMAP
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed Ref.1

Chain

2 – 438

437

Coenzyme A disulfide reductase HAMAP MF_01608

PRO_0000184688

Regions

Nucleotide binding

8 – 33

26

FAD HAMAP MF_01608

Nucleotide binding

151 – 166

16

NADP By similarity

Nucleotide binding

267 – 277

11

FAD HAMAP MF_01608

Sites

Active site

43

1

Nucleophile Ref.4

Active site

43

1

Redox-active Ref.4

Binding site

15

1

Substrate HAMAP MF_01608

Binding site

19

1

Substrate HAMAP MF_01608

Binding site

22

1

Substrate HAMAP MF_01608

Binding site

39

1

Substrate HAMAP MF_01608

Binding site

42

1

Substrate HAMAP MF_01608

Binding site

71

1

Substrate HAMAP MF_01608

Binding site

299

1

Substrate HAMAP MF_01608

Binding site

419

1

FAD; via carbonyl oxygen HAMAP MF_01608

Binding site

427

1

Substrate HAMAP MF_01608

Experimental info

Mutagenesis

43

1

C → S: Loss of activity. Ref.4

Mutagenesis

361

1

Y → F: Reduces activity by 92%. Loss of activity; when associated with F-419. Ref.5

Mutagenesis

419

1

Y → F: Reduces activity by 80%. Loss of activity; when associated with F-361. Ref.5

Secondary structure

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438

Helix Strand Turn

Details...

Beta strand

4 – 7

4

Helix

13 – 23

11

Beta strand

25 – 27

3

Beta strand

29 – 36

8

Beta strand

38 – 40

3

Helix

42 – 44

3

Helix

45 – 49

5

Helix

56 – 59

4

Helix

64 – 71

8

Beta strand

74 – 77

4

Beta strand

79 – 85

7

Turn

86 – 89

4

Beta strand

90 – 95

6

Turn

96 – 99

4

Beta strand

100 – 105

6

Beta strand

107 – 111

5

Beta strand

115 – 117

3

Helix

133 – 146

14

Beta strand

150 – 154

5

Helix

158 – 170

13

Beta strand

173 – 181

9

Helix

189 – 192

4

Helix

193 – 201

9

Beta strand

206 – 209

4

Beta strand

212 – 216

5

Beta strand

219 – 222

4

Beta strand

227 – 229

3

Beta strand

231 – 235

5

Beta strand

239 – 242

4

Helix

244 – 246

3

Beta strand

272 – 274

3

Helix

276 – 278

3

Beta strand

279 – 290

12

Helix

295 – 310

16

Beta strand

324 – 328

5

Beta strand

331 – 338

8

Helix

340 – 345

6

Beta strand

348 – 358

11

Beta strand

362 – 364

3

Beta strand

367 – 375

9

Turn

376 – 378

3

Beta strand

380 – 391

12

Helix

392 – 404

13

Helix

410 – 414

5

Turn

421 – 423

3

Helix

429 – 435

7

Sequences

	Sequence		Length	Mass (Da)
	O52582-1 [UniParc]. Last modified January 23, 2007. Version 3. Checksum: 3A9B643BD8D44402	FASTA	438	49,241
	10 20 30 40 50 60 MPKIVVVGAV AGGATCASQI RRLDKESDII IFEKDRDMSF ANCALPYVIG EVVEDRRYAL 70 80 90 100 110 120 AYTPEKFYDR KQITVKTYHE VIAINDERQT VSVLNRKTNE QFEESYDKLI LSPGASANSL 130 140 150 160 170 180 GFESDITFTL RNLEDTDAID QFIKANQVDK VLVVGAGYVS LEVLENLNER GLHPTLIHRS 190 200 210 220 230 240 DKINKLMDAD MNQPILDELD KREIPYRLNE EINAINGNEI TFKSGKVEHY DMIIEGVGTH 250 260 270 280 290 300 PNSKFIESSN IKLDRKGFIP VNDKFETNVP NIYAIGDIAT SHYRHVDLPA SVPLAWGAHR 310 320 330 340 350 360 AASIVAEQIA GNDTIEFKGF LGNNIVKFFD YTFASVGVKP NELKQFDYKM VEVTQGAHAN 370 380 390 400 410 420 YYPGNSPLHL RVYYDTSNRQ ILRAAAVGKE GADKRIDVLS MAMMNQLTVD ELTEFEVAYA 430 PPYSHPKDLI NMIGYKAK

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Staphylococcus aureus coenzyme A disulfide reductase, a new subfamily of pyridine nucleotide-disulfide oxidoreductase. Sequence, expression, and analysis of cdr." delCardayre S.B., Davies J.E. J. Biol. Chem. 273:5752-5757(1998) [PubMed: 9488708] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], PROTEIN SEQUENCE OF 2-15 AND 193-208.
[2]	"The Staphylococcus aureus NCTC8325 genome." Gillaspy A.F., Worrell V., Orvis J., Roe B.A., Dyer D.W., Iandolo J.J. Submitted (JAN-2006) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]	"Coenzyme A disulfide reductase, the primary low molecular weight disulfide reductase from Staphylococcus aureus. Purification and characterization of the native enzyme." delCardayre S.B., Stock K.P., Newton G.L., Fahey R.C., Davies J.E. J. Biol. Chem. 273:5744-5751(1998) [PubMed: 9488707] [Abstract] Cited for: CHARACTERIZATION.
[4]	"Coenzyme A-disulfide reductase from Staphylococcus aureus: evidence for asymmetric behavior on interaction with pyridine nucleotides." Luba J., Charrier V., Claiborne A. Biochemistry 38:2725-2737(1999) [PubMed: 10052943] [Abstract] Cited for: CHARACTERIZATION, ACTIVE SITE, MUTAGENESIS OF CYS-43, MASS SPECTROMETRY.
[5]	"Structure of coenzyme A-disulfide reductase from Staphylococcus aureus at 1.54 A resolution." Mallett T.C., Wallen J.R., Karplus P.A., Sakai H., Tsukihara T., Claiborne A. Biochemistry 45:11278-11289(2006) [PubMed: 16981688] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.54 ANGSTROMS) IN COMPLEX WITH FAD AND SUBSTRATE, MUTAGENESIS OF TYR-361 AND TYR-419, SUBUNIT.

Cross-references

Sequence databases

EMBLGenBankDDBJ

AF041467 Genomic DNA. Translation: AAB97073.1.
CP000253 Genomic DNA. Translation: ABD30033.1.

RefSeq

YP_499461.1.

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1YQZ	X-ray	1.54	A/B	1-438	[»]

ModBase

Search...

Genome annotation databases

GeneID

3920795.

GenomeReviews

Gene locus SAOUHSC_00908 in contig CP000253_GR.

KEGG

sao:SAOUHSC_00908.

Organism-specific databases

CMR

Search...

Phylogenomic databases

HOGENOM

O52582.

Enzyme and pathway databases

BioCyc

SAUR93061:SAOUHSC_00908-MON.

Family and domain databases

HAMAP

MF_01608.
[Tree]

InterPro

IPR017758. CoA_disulphide_reductase.
IPR013027. FAD_pyr_nucl-diS_OxRdtase.
IPR004099. Pyr_nucl-diS_OxRdtase_dimer.
IPR001327. Pyr_OxRdtase_NAD_bd.
[Graphical view]

Gene3D

G3DSA:3.30.390.30. Pyr_redox_dim. 1 hit.

Pfam

PF00070. Pyr_redox. 1 hit.
PF07992. Pyr_redox_2. 1 hit.
PF02852. Pyr_redox_dim. 1 hit.
[Graphical view]

PRINTS

PR00368. FADPNR.

ProDom

PD000139. FAD_pyr_redox. 1 hit.
[Graphical view] [Entries sharing at least one domain]

TIGRFAMs

TIGR03385. CoA_CoA_reduc. 1 hit.

ProtoNet

Search...

Entry information

Entry name

CDR_STAA8

Accession

Primary (citable) accession number: O52582
Secondary accession number(s): Q2FZT2

Entry history

Integrated into UniProtKB/Swiss-Prot:	March 1, 2005
Last sequence update:	January 23, 2007
Last modified:	June 16, 2009
This is version 58 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HAMAP (High-quality Automated and Manual Annotation of microbial Proteomes)