TB Genome Annotation Portal

Rv1240 (mdh)

• Current annotations:
  • TBCAP: (community-based annotations - see table at bottom of page)
  • TBDB: malate dehydrogenase
  • REFSEQ: malate dehydrogenase
  • PATRIC: Malate dehydrogenase (EC 1.1.1.37)
  • TUBERCULIST: Probable malate dehydrogenase Mdh
  • NCBI: Probable malate dehydrogenase Mdh
  • updated information (H37Rv4):
    • gene name: mdh
    • function:
    • reference: Harold (2022) PMID: 35337802
• Type: Not Target
• Start: 1383213
• End: 1384202
• Operon:


• Trans-membrane region:
  
• Role: I.B.3 - TCA cycle
• GO terms:
  • GO:0055114 - oxidation-reduction process (Uniprot)
  • GO:0030060 - L-malate dehydrogenase activity (Uniprot)
  • GO:0019752 - carboxylic acid metabolic process (Uniprot)
  • GO:0016616 - oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor (Uniprot)
  • GO:0016615 - malate dehydrogenase activity (Uniprot)
  • GO:0016491 - oxidoreductase activity (Uniprot)
  • GO:0006734 - NADH metabolic process (Uniprot)
  • GO:0006108 - malate metabolic process (Uniprot)
  • GO:0006107 - oxaloacetate metabolic process (Uniprot)
  • GO:0006099 - tricarboxylic acid cycle (Uniprot)
  • GO:0005975 - carbohydrate metabolic process (Uniprot)
  • GO:0005886 - plasma membrane (Uniprot)
  • GO:0005829 - cytosol (Uniprot)
  • GO:0005618 - cell wall (Uniprot)
  • GO:0003824 - catalytic activity (Uniprot)
• Reaction(s) (based on iSM810 metabolic model):
  • NAD[c] + MAL[c] <=> NADH[c] + OA[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:
• Search for Homologs in PDB
• Top 10 Homologs in PDB (as of Nov 2020):
  

  PDB	aa ident	species	PDB title
  5KVV	100%	Mycobacterium tuberculosis	Structure of Malate Dehydrogenase in complex with NADH from Mycobacterium tuberculosis
  4TVO	100%	Mycobacterium tuberculosis	Structure of Malate Dehydrogenase from Mycobacterium tuberculosis
  4KDF	63%	Thermus thermophilus	Crystal Structure of Thermus thermophilus Malate Dehydrogenase in Complex with NAD
  4KDE	63%	Thermus thermophilus	Crystal Structure of the Apo Form of Thermus thermophilus Malate Dehydrogenase
  2CVQ	63%	Thermus thermophilus	Crystal structure of NAD(H)-dependent malate dehydrogenase complexed with NADPH
  1Y7T	63%	Thermus thermophilus	Crystal structure of NAD(H)-depenent malate dehydrogenase complexed with NADPH
  1IZ9	63%	Thermus thermophilus	Crystal Structure of Malate Dehydrogenase from Thermus thermophilus HB8
  1BMD	63%	Thermus thermophilus	DETERMINANTS OF PROTEIN THERMOSTABILITY OBSERVED IN THE 1.9 ANGSTROMS CRYSTAL STRUCTURE OF MALATE DEHYDROGENASE FROM THE THERMOPHILIC BACTERIUM THERMUS FLAVUS
  1WZI	63%	Thermus thermophilus	Structural basis for alteration of cofactor specificity of Malate dehydrogenase from Thermus flavus
  1WZE	63%	Thermus thermophilus	Structural basis for alteration of cofactor specificity of Malate dehydrogenase from Thermus flavus

• Links to additional information on mdh:
  • KEGG - nucleotide and amino acid sequences of gene
  • Mycobrowser
  • PATRIC
  • BioCyc
  • Systems Biology
  • TBDB (updated)
  • Phyre2 structure prediction, model: final.casp.pdb (from Mao et al, 2013)
  • UniProt
  • AlphaFold model
  • Vulnerability = -6.304 (from Jeremy Rock's lab)

Amino Acid Sequence

VSASPLKVAVTGAAGQIGYSLLFRLASGSLLGPDRPIELRLLEIEPALQALEGVVMELDDCAFPLLSGVEIGSDPQKIFDGVSLALLVGARPRGAGMERS
DLLEANGAIFTAQGKALNAVAADDVRVGVTGNPANTNALIAMTNAPDIPRERFSALTRLDHNRAISQLAAKTGAAVTDIKKMTIWGNHSATQYPDLFHAE
VAGKNAAEVVNDQAWIEDEFIPTVAKRGAAIIDARGASSAASAASATIDAARDWLLGTPADDWVSMAVVSDGSYGVPEGLISSFPVTTKGGNWTIVSGLE
IDEFSRGRIDKSTAELADERSAVTELGLI

Additional Information

Analysis of Positive Selection in Clinical Isolates *new*

• Analysis of dN/dS (omega) in two collections of Mtb clinical isolates using GenomegaMap (Window model) (see description of methods)
  • Moldova: 2,057 clinical isolates
  • global set: 5,195 clinical isolates from 15 other countries
• In the omega plots, the black line shows the mean estimate of omega (dN/dS) at each codon, and the blue lines are the bounds for the 95% credible interval (95%CI, from MCMC sampling).
• A gene is under significant positive selection if the lower-bound of the 95%CI of omega (lower blue line) exceeds 1.0 at any codon.

	Moldova (2,057)	global set (5,195)
under significant positive selection?	NO	NO
omega peak height (95%CI lower bound)	1.9 (0.33)	1.25 (0.4)
codons under selection
omega plots
genetic variants*	link	link
statistics at each codon	link	link