TB Genome Annotation Portal

Rv2332 (mez)

• Current annotations:
  • TBCAP: (community-based annotations - see table at bottom of page)
  • TBDB: malate dehydrogenase (oxaloacetate-decarboxylating)
  • REFSEQ: malate dehydrogenase
  • PATRIC: NAD-dependent malic enzyme (EC 1.1.1.38)
  • TUBERCULIST: Probable [NAD] dependent malate oxidoreductase Mez (malic enzyme) (NAD-malic enzyme) (malate dehydrogenase (oxaloacetate decarboxylating)) (pyruvic-malic carboxylase) (NAD-me)
  • NCBI: Probable [NAD] dependent malate oxidoreductase Mez (malic enzyme) (NAD-malic enzyme) (malate dehydrogenase (oxaloacetate decarboxylating)) (pyruvic-malic carboxylase) (NAD-me)
  • updated information (H37Rv4):
    • gene name: mez
    • function:
    • reference:
• Type: Not Target
• Start: 2605108
• End: 2606754
• Operon:


• Trans-membrane region:
  
• Role: I.B.7 - Miscellaneous oxidoreductases and oxygenases
• GO terms:
  • GO:0055114 - oxidation-reduction process (Uniprot)
  • GO:0051287 - NAD binding (Uniprot)
  • GO:0046872 - metal ion binding (Uniprot)
  • GO:0016491 - oxidoreductase activity (Uniprot)
  • GO:0008948 - oxaloacetate decarboxylase activity (Uniprot)
  • GO:0006108 - malate metabolic process (Uniprot)
  • GO:0006090 - pyruvate metabolic process (Uniprot)
  • GO:0005829 - cytosol (Uniprot)
  • GO:0004471 - malate dehydrogenase (decarboxylating) (NAD+) activity (Uniprot)
  • GO:0004470 - malic enzyme activity (Uniprot)
• Reaction(s) (based on iSM810 metabolic model):
  • NAD[c] + MAL[c] <=> NADH[c] + CO2[c] + PYR[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
  6URF	100%	Mycobacterium tuberculosis	Malic enzyme from Mycobacterium tuberculosis
  6AGS	41%	Escherichia coli	Structural insights for non-natural cofactor binding by the L310R/Q401C mutant of malic enzyme from Escherichia coli
  6C7N	39%	Sorghum bicolor	Monoclinic form of malic enzyme from sorghum at 2 angstroms resolution
  5OU5	39%	Zea mays	Crystal structure of maize chloroplastic photosynthetic NADP(+)-dependent malic enzyme
  1O0S	39%	Ascaris suum	Crystal Structure of Ascaris suum Malic Enzyme Complexed with NADH
  1LLQ	39%	Ascaris suum	Crystal Structure of Malic Enzyme from Ascaris suum Complexed with Nicotinamide Adenine Dinucleotide
  1GQ2	39%	COLUMBA LIVIA	Malic Enzyme from Pigeon Liver
  3WJA	38%	Homo sapiens	The crystal structure of human cytosolic NADP(+)-dependent malic enzyme in apo form
  2AW5	38%	Homo sapiens	Crystal structure of a human malic enzyme
  1QR6	36%	Homo sapiens	HUMAN MITOCHONDRIAL NAD(P)-DEPENDENT MALIC ENZYME

• Links to additional information on mez:
  • 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 = 1.46 (from Jeremy Rock's lab)

Amino Acid Sequence

MSDARVPRIPAALSAPSLNRGVGFTHAQRRRLGLTGRLPSAVLTLDQQAERVWHQLQSLATELGRNLLLEQLHYRHEVLYFKVLADHLPELMPVVYTPTV
GEAIQRFSDEYRGQRGLFLSIDEPDEIEEAFNTLGLGPEDVDLIVCTDAEAILGIGDWGVGGIQIAVGKLALYTAGGGVDPRRCLAVSLDVGTDNEQLLA
DPFYLGNRHARRRGREYDEFVSRYIETAQRLFPRAILHFEDFGPANARKILDTYGTDYCVFNDDMQGTGAVVLAAVYSGLKVTGIPLRDQTIVVFGAGTA
GMGIADQIRDAMVADGATLEQAVSQIWPIDRPGLLFDDMDDLRDFQVPYAKNRHQLGVAVGDRVGLSDAIKIASPTILLGCSTVYGAFTKEVVEAMTASC
KHPMIFPLSNPTSRMEAIPADVLAWSNGRALLATGSPVAPVEFDETTYVIGQANNVLAFPGIGLGVIVAGARLITRRMLHAAAKAIAHQANPTNPGDSLL
PDVQNLRAISTTVAEAVYRAAVQDGVASRTHDDVRQAIVDTMWLPAYD

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)	1.83 (0.43)	2.07 (0.82)
codons under selection
omega plots
genetic variants*	link	link
statistics at each codon	link	link