Rv3303c (lpdA)

Current annotations:
- TBCAP: (community-based annotations - see table at bottom of page)
- TBDB: NAD(P)H dehydrogenase (quinone)
- REFSEQ: flavoprotein disulfide reductase
- PATRIC: Dihydrolipoamide dehydrogenase (EC 1.8.1.4)
- TUBERCULIST: NAD(P)H quinone reductase LpdA
- NCBI: NAD(P)H quinone reductase LpdA
- updated information (H37Rv4):
  - gene name: lpdA
  - function: probably a flavoprotein disulfide reductase (not a lipoamide dehydrogenase)
  - reference: Argyrou (2004) PMID: 15456792
Type: Not Target
Start: 3689457
End: 3690938
Operon:

Trans-membrane region:
Role: I.B.2 - Pyruvate dehydrogenase
GO terms:
- GO:0070401 - NADP+ binding (Uniprot)
- GO:0055114 - oxidation-reduction process (Uniprot)
- GO:0050660 - flavin adenine dinucleotide binding (Uniprot)
- GO:0045454 - cell redox homeostasis (Uniprot)
- GO:0022900 - electron transport chain (Uniprot)
- GO:0016655 - oxidoreductase activity, acting on NAD(P)H, quinone or similar compound as acceptor (Uniprot)
- GO:0016491 - oxidoreductase activity (Uniprot)
- GO:0009405 - pathogenesis (Uniprot)
- GO:0009055 - electron transfer activity (Uniprot)
- GO:0005623 - cell (Uniprot)
- GO:0003955 - NAD(P)H dehydrogenase (quinone) activity (Uniprot)
Reaction(s) (based on iSM810 metabolic model):
- NAD[c] + NADPH[c] -> NADH[c] + NADP[c]
Gene Expression Profile (Transcriptional Responses to Drugs; Boshoff et al, 2004)
Gene Modules extracted from cluster analysis of 249 transcriptomic datasets using ICA
Orthologs among selected mycobacteria
Protein structure: 1xdi
Search for Homologs in PDB
Top 10 Homologs in PDB (as of Nov 2020):

PDB aa ident species PDB title

1XDI 100% Mycobacterium tuberculosis Crystal structure of LpdA (Rv3303c) from Mycobacterium tuberculosis
Links to additional information on lpdA:
- TBDB (updated)
- Phyre2 structure prediction, model: final.casp.pdb (from Mao et al, 2013)
- UniProt
- AlphaFold model
- Vulnerability = -12.303 (from Jeremy Rock's lab)
- KEGG - nucleotide and amino acid sequences of gene
- Mycobrowser
- PATRIC
- BioCyc
- Systems Biology

PDB	aa ident	species	PDB title
1XDI	100%	Mycobacterium tuberculosis	Crystal structure of LpdA (Rv3303c) from Mycobacterium tuberculosis

Amino Acid Sequence

VVTRIVILGGGPAGYEAALVAATSHPETTQVTVIDCDGIGGAAVLDDCVPSKTFIASTGLRTELRRAPHLGFHIDFDDAKISLPQIHARVKTLAAAQSAD
ITAQLLSMGVQVIAGRGELIDSTPGLARHRIKATAADGSTSEHEADVVLVATGASPRILPSAQPDGERILTWRQLYDLDALPDHLIVVGSGVTGAEFVDA
YTELGVPVTVVASQDHVLPYEDADAALVLEESFAERGVRLFKNARAASVTRTGAGVLVTMTDGRTVEGSHALMTIGSVPNTSGLGLERVGIQLGRGNYLT
VDRVSRTLATGIYAAGDCTGLLPLASVAAMQGRIAMYHALGEGVSPIRLRTVAATVFTRPEIAAVGVPQSVIDAGSVAARTIMLPLRTNARAKMSEMRHG
FVKIFCRRSTGVVIGGVVVAPIASELILPIAVAVQNRITVNELAQTLAVYPSLSGSITEAARRLMAHDDLDCTAAQDAAEQLALVPHHLPTSN

(Nucleotide sequence available on KEGG)

Additional Information

probably a flavoprotein disulfide reductase (not a lipoamide dehydrogenase)
Argyrou, Vetting, and Blanchard (2004). JBC. http://www.jbc.org/content/279/50/52694.full

ESSENTIALITY

MtbTnDB - interactive tool for exploring a database of published TnSeq datasets for Mtb

TnSeqCorr - genes with correlated TnSeq profiles across >100 conditions *new*

Classification	Condition	Strain	Method	Reference	Notes
Essential	Sodium Oleate	H37RvMA	Gumbel	Subhalaxmi Nambi	Probability of Essentiality: 0.999950; 19 non-insertions in a row out of 22 sites
Uncertain	Lignoceric Acid	H37RvMA	Gumbel	Subhalaxmi Nambi	Probability of Essentiality: 0.943000; 8 non-insertions in a row out of 22 sites
Non-Essential	Phosphatidylcholine	H37RvMA	Gumbel	Subhalaxmi Nambi	Probability of Essentiality: 0.000000; 4 non-insertions in a row out of 22 sites
Uncertain	minimal media + 0.1% glycerol	H37RvMA	Gumbel	Griffin et al. (2011)	Probability of Essentiality: 0.929500; 8 non-insertions in a row out of 22 sites
Non-Essential	minimal media + 0.01% cholesterol	H37RvMA	Gumbel	Griffin et al. (2011)	Probability of Essentiality: 0.000000; 4 non-insertions in a row out of 22 sites
Non-Essential	7H10-glycerol	H37RvMA	TraSH	Sassetti et al. (2003a)
Non-Essential	C57BL/6J mice (8 weeks)	H37RvMA	TraSH	Sassetti et al. (2003b)	Hybridization Ratio: 0.74
Non-Essential	7H09/7H10 + rich media	H37RvMA	MotifHMM	DeJesus et al. (2017)	Fully saturated (14 reps).

TnSeq Data No data currently available.

No TnSeq data currently available for this Target.

RNASeq Data No data currently available.

No RNA-Seq data currently available for this Target.

Metabolomic Profiles No data currently available.

No Metabolomic data currently available for this Target.

Proteomic Data No data currently available.

No Proteomic data currently available for this Target.

Regulatory Relationships from Systems Biology

BioCyc

Gene interactions based on ChIPSeq and Transcription Factor Over-Expression (TFOE) (Systems Biology)

NOTE: Green edges represent the connected genes being classified as differentially essential as a result of the middle gene being knocked out. These interactions are inferred based on RNASeq.

Interactions based on ChIPSeq data

Binds To:
- No bindings to other targets were found.
Bound By:
- Rv0818 (-)
- Rv2989 (-)

Interactions based on ChIPSeq data (Minch et al. 2014)

Binds To:
- No bindings to other targets were found.
Bound By:
- Rv1719 (-) (Direct binding)
- Rv2989 (-) (Direct binding)

Interactions based on TFOE data (Rustad et al. 2014)

Upregulates:
- Does not upregulate other genes.
Upregulated by:
- Not upregulated by other genes.
Downregulates:
- Does not downregulate other genes.
Downregulated by:
- Rv0818 (-)
- Rv2989 (-)

Property	Value	Creator	Evidence	PMID	Comment
Citation	Characterization of a new member of the flavoprotein disulfide reductase family of enzymes from Mycobacterium tuberculosis. A. Argyrou, MW. Vetting et al. J. Biol. Chem. 2004	jjmcfadden		15456792	Inferred from direct assay
Term	EC:1.6.1.1 NAD(P)(+) transhydrogenase (B-specific). - NR	jjmcfadden	NR		Inferred from direct assay A. Argyrou, MW. Vetting et al. Characterization of a new member of the flavoprotein disulfide reductase family of enzymes from Mycobacterium tuberculosis. J. Biol. Chem. 2004
Term	EC:1.8.1.4 Dihydrolipoyl dehydrogenase. - NR	jjmcfadden	NR		Inferred from direct assay A. Argyrou, MW. Vetting et al. Characterization of a new member of the flavoprotein disulfide reductase family of enzymes from Mycobacterium tuberculosis. J. Biol. Chem. 2004
Term	EC:1.6.5.2 NAD(P)H dehydrogenase (quinone). - NR	jjmcfadden	NR		Inferred from direct assay A. Argyrou, MW. Vetting et al. Characterization of a new member of the flavoprotein disulfide reductase family of enzymes from Mycobacterium tuberculosis. J. Biol. Chem. 2004

TB Genome Annotation Portal