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P66004 (DLDH_MYCTU) Reviewed, UniProtKB/Swiss-Prot

Last modified January 25, 2012. Version 65. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
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to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Dihydrolipoyl dehydrogenase
EC=1.8.1.4
Alternative name(s):
Dihydrolipoamide dehydrogenase
E3 component of alpha keto acid dehydrogenase complexes
Gene names
Name:lpd
Ordered Locus Names:Rv0462, MT0478
ORF Names:MTV038.06
OrganismMycobacterium tuberculosis
Taxonomic identifier1773 [NCBI]
Taxonomic lineageBacteria › Actinobacteria › Actinobacteridae › Actinomycetales › Corynebacterineae › Mycobacteriaceae › Mycobacterium › Mycobacterium tuberculosis complex

Protein attributes

Sequence length464 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Lipoamide dehydrogenase is a component of the alpha-ketoacid dehydrogenase complexes. Together with AhpD, DltA and Lpd constitutes an NADH-dependent peroxidase active against hydrogen and alkyl peroxides as well as serving as a peroxynitrite reductase, thus protecting the bacterium against reactive nitrogen intermediates and oxidative stress generated by the host immune system. Ref.3 Ref.4

Catalytic activity

Protein N(6)-(dihydrolipoyl)lysine + NAD+ = protein N(6)-(lipoyl)lysine + NADH.

Cofactor

Binds 1 FAD per subunit.

Subunit structure

Homodimer. Identified in a complex with AhpC, AhpD and DltA. Ref.3 Ref.4

Subcellular location

Cytoplasm Potential.

Miscellaneous

The active site is a redox-active disulfide bond.

Sequence similarities

Belongs to the class-I pyridine nucleotide-disulfide oxidoreductase family.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 464464Dihydrolipoyl dehydrogenase
PRO_0000068034

Regions

Nucleotide binding33 – 419FAD
Nucleotide binding178 – 1825NAD By similarity
Nucleotide binding266 – 2694NAD By similarity

Sites

Active site4431Proton acceptor By similarity
Binding site501FAD
Binding site1131FAD; via amide nitrogen and carbonyl oxygen By similarity
Binding site2011NAD By similarity
Binding site3091FAD
Binding site3171FAD; via amide nitrogen

Amino acid modifications

Disulfide bond41 ↔ 46Redox-active Ref.4

Experimental info

Mutagenesis51D → A: Reduces lipoamide dehydrogenase activity by 95%. Ref.4
Mutagenesis431N → A: Reduces lipoamide dehydrogenase activity by 89%. Ref.4
Mutagenesis931R → A: Reduces lipoamide dehydrogenase activity by 94%. Ref.4
Mutagenesis931R → E: Reduces lipoamide dehydrogenase activity by 96%. Ref.4
Mutagenesis1031K → E: Reduces lipoamide dehydrogenase activity by 82%. Ref.4
Mutagenesis3861H → K: Reduces lipoamide dehydrogenase activity by 91%. Ref.4
Mutagenesis4641F → A: Reduces lipoamide dehydrogenase activity by 95%. Ref.4

Secondary structure

1 ................................................................................. 464
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P66004 [UniParc].

Last modified October 11, 2004. Version 1.
Checksum: DD93D95DC6F76B22

FASTA46449,239
        10         20         30         40         50         60 
MTHYDVVVLG AGPGGYVAAI RAAQLGLSTA IVEPKYWGGV CLNVGCIPSK ALLRNAELVH 

        70         80         90        100        110        120 
IFTKDAKAFG ISGEVTFDYG IAYDRSRKVA EGRVAGVHFL MKKNKITEIH GYGTFADANT 

       130        140        150        160        170        180 
LLVDLNDGGT ESVTFDNAII ATGSSTRLVP GTSLSANVVT YEEQILSREL PKSIIIAGAG 

       190        200        210        220        230        240 
AIGMEFGYVL KNYGVDVTIV EFLPRALPNE DADVSKEIEK QFKKLGVTIL TATKVESIAD 

       250        260        270        280        290        300 
GGSQVTVTVT KDGVAQELKA EKVLQAIGFA PNVEGYGLDK AGVALTDRKA IGVDDYMRTN 

       310        320        330        340        350        360 
VGHIYAIGDV NGLLQLAHVA EAQGVVAAET IAGAETLTLG DHRMLPRATF CQPNVASFGL 

       370        380        390        400        410        420 
TEQQARNEGY DVVVAKFPFT ANAKAHGVGD PSGFVKLVAD AKHGELLGGH LVGHDVAELL 

       430        440        450        460 
PELTLAQRWD LTASELARNV HTHPTMSEAL QECFHGLVGH MINF

« Hide

References

« Hide '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. expand/collapse author list , 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: 9634230] [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. expand/collapse author list , 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: 12218036] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Strain: CDC 1551 / Oshkosh.
[3]"Metabolic enzymes of mycobacteria linked to antioxidant defense by a thioredoxin-like protein."
Bryk R., Lima C.D., Erdjument-Bromage H., Tempst P., Nathan C.
Science 295:1073-1077(2002) [PubMed: 11799204] [Abstract]
Cited for: FUNCTION AS AN ANTIOXIDANT, SUBUNIT.
Strain: ATCC 25618 / H37Rv.
[4]"Crystal structure and functional analysis of lipoamide dehydrogenase from Mycobacterium tuberculosis."
Rajashankar K.R., Bryk R., Kniewel R., Buglino J.A., Nathan C.F., Lima C.D.
J. Biol. Chem. 280:33977-33983(2005) [PubMed: 16093239] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) IN COMPLEX WITH FAD, DISULFIDE BOND, SUBUNIT, FUNCTION, MUTAGENESIS OF ASP-5; ASN-43; ARG-93; LYS-103; HIS-386 AND PHE-464.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ		BX842573 Genomic DNA. Translation: CAA17417.1.
AE000516 Genomic DNA. Translation: AAK44702.1.
PIRB70828.
RefSeqNP_214976.1. NC_000962.2.
NP_334888.1. NC_002755.2.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2A8XX-ray2.40A/B1-464[»]
3II4X-ray2.42A/B1-464[»]
ProteinModelPortalP66004.
SMRP66004. Positions 1-464.
ModBaseSearch...

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblBacteriaEBMYCT00000002557; EBMYCP00000002557; EBMYCG00000002555.
EBMYCT00000070711; EBMYCP00000068770; EBMYCG00000070706.
GeneID886300.
923824.
GenomeReviewsGene locus MT0478 in contig AE000516_GR.
Gene locus Rv0462 in contig AL123456_GR.
KEGGmtc:MT0478.
mtu:Rv0462.
PATRIC18122764. VBIMycTub22151_0516.
TIGRMT0478.

Organism-specific databases

TubercuListRv0462.

Phylogenomic databases

GeneTreeEBGT00050000014575.
HOGENOMHBG515043.
OMAFAPRVEG.
PhylomeDBP66004.
ProtClustDBPRK07818.

Family and domain databases

InterProIPR016156. FAD/NAD-linked_Rdtase_dimer.
IPR013027. FAD_pyr_nucl-diS_OxRdtase.
IPR006258. Lipoamide_DH.
IPR004099. Pyr_nucl-diS_OxRdtase_dimer.
IPR023753. Pyr_nucl-diS_OxRdtase_FAD/NAD.
IPR012999. Pyr_OxRdtase_I_AS.
IPR001327. Pyr_OxRdtase_NAD-bd_dom.
[Graphical view]
Gene3DG3DSA:3.30.390.30. Pyr_redox_dim. 1 hit.
KOK00382.
PfamPF00070. Pyr_redox. 1 hit.
PF07992. Pyr_redox_2. 1 hit.
PF02852. Pyr_redox_dim. 1 hit.
[Graphical view]
PRINTSPR00368. FADPNR.
SUPFAMSSF55424. FAD/NAD-linked_reductase_dimer. 1 hit.
TIGRFAMsTIGR01350. Lipoamide_DH. 1 hit.
PROSITEPS00076. PYRIDINE_REDOX_1. 1 hit.
[Graphical view]
ProtoNetSearch...

Entry information

Entry nameDLDH_MYCTU
AccessionPrimary (citable) accession number: P66004
Secondary accession number(s): O53747
Entry history
Integrated into UniProtKB/Swiss-Prot: October 11, 2004
Last sequence update: October 11, 2004
Last modified: January 25, 2012
This is version 65 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programProkaryotic Protein Annotation Program

Relevant documents

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

SIMILARITY comments

Index of protein domains and families

to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents