Molecule Information

General Information of the Molecule (ID: Mol01052)

• Name: Probable arabinosyltransferase B (EMBB) ,Mycobacteriumtuberculosis
• Synonyms: Rv3795; MTCY13D12.29
• Molecule Type: Protein
• Gene Name: embB
• Gene ID: 886126
• Sequence:
  MTQCASRRKSTPNRAILGAFASARGTRWVATIAGLIGFVLSVATPLLPVVQTTAMLDWPQ
  RGQLGSVTAPLISLTPVDFTATVPCDVVRAMPPAGGVVLGTAPKQGKDANLQALFVVVSA
  QRVDVTDRNVVILSVPREQVTSPQCQRIEVTSTHAGTFANFVGLKDPSGAPLRSGFPDPN
  LRPQIVGVFTDLTGPAPPGLAVSATIDTRFSTRPTTLKLLAIIGAIVATVVALIALWRLD
  QLDGRGSIAQLLLRPFRPASSPGGMRRLIPASWRTFTLTDAVVIFGFLLWHVIGANSSDD
  GYILGMARVADHAGYMSNYFRWFGSPEDPFGWYYNLLALMTHVSDASLWMRLPDLAAGLV
  CWLLLSREVLPRLGPAVEASKPAYWAAAMVLLTAWMPFNNGLRPEGIIALGSLVTYVLIE
  RSMRYSRLTPAALAVVTAAFTLGVQPTGLIAVAALVAGGRPMLRILVRRHRLVGTLPLVS
  PMLAAGTVILTVVFADQTLSTVLEATRVRAKIGPSQAWYTENLRYYYLILPTVDGSLSRR
  FGFLITALCLFTAVFIMLRRKRIPSVARGPAWRLMGVIFGTMFFLMFTPTKWVHHFGLFA
  AVGAAMAALTTVLVSPSVLRWSRNRMAFLAALFFLLALCWATTNGWWYVSSYGVPFNSAM
  PKIDGITVSTIFFALFAIAAGYAAWLHFAPRGAGEGRLIRALTTAPVPIVAGFMAAVFVA
  SMVAGIVRQYPTYSNGWSNVRAFVGGCGLADDVLVEPDTNAGFMKPLDGDSGSWGPLGPL
  GGVNPVGFTPNGVPEHTVAEAIVMKPNQPGTDYDWDAPTKLTSPGINGSTVPLPYGLDPA
  RVPLAGTYTTGAQQQSTLVSAWYLLPKPDDGHPLVVVTAAGKIAGNSVLHGYTPGQTVVL
  EYAMPGPGALVPAGRMVPDDLYGEQPKAWRNLRFARAKMPADAVAVRVVAEDLSLTPEDW
  IAVTPPRVPDLRSLQEYVGSTQPVLLDWAVGLAFPCQQPMLHANGIAEIPKFRITPDYSA
  KKLDTDTWEDGTNGGLLGITDLLLRAHVMATYLSRDWARDWGSLRKFDTLVDAPPAQLEL
  GTATRSGLWSPGKIRIGP
• 3D-structure: PDB ID: 7BVF; Classification: Transferase; Method: Electron microscopy; Resolution: 2.97 Å
• Function: Arabinosyl transferase responsible for the polymerization of arabinose into the arabinan of arabinogalactan.
• Uniprot ID: EMBB_MYCTU

Kingdom: N.A.
Phylum: Actinobacteria
Class: Actinomycetia
Order: Corynebacteriales
Family: Mycobacteriaceae
Genus: Mycobacterium
Species: Mycobacterium tuberculosis

Type(s) of Resistant Mechanism of This Molecule

  ADTT: Aberration of the Drug's Therapeutic Target

  EADR: Epigenetic Alteration of DNA, RNA or Protein

  UAPP: Unusual Activation of Pro-survival Pathway

Drug Resistance Data Categorized by Drug

Approved Drug(s) 2 drug(s) in total

Ethambutol

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Disease Class: Tuberculosis [ICD-11: 1B10.0] [1]

• Resistant Disease: Tuberculosis [ICD-11: 1B10.0]
• Resistant Drug: Ethambutol
• Molecule Alteration: Mutation; .
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: STK11 KO cells; Fetal kidney; Homo sapiens (Human); CVCL_B3IE
• Mechanism Description: Ethambutol (EMB) is one of the first-line drugs regimens for TB treatment. Arabinosyl transferases are established targets of EMB, which is involved in the biosynthesis of arabinogalactan (AG) and lipoarabinomannan (LAM). Mutations among embCAB operon are responsible for around 70% clinical EMB resistant M. tuberculosis.

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Disease Class: Tuberculosis [ICD-11: 1B10.0] [2]

• Resistant Disease: Tuberculosis [ICD-11: 1B10.0]
• Resistant Drug: Ethambutol
• Molecule Alteration: Mutation; R173C
• Experimental Note: Revealed Based on the Cell Line Data
• Experiment for Molecule Alteration: GeneSeq assay; Bioinformatics assay
• Mechanism Description: Out of total 112 mycobacterial positive cultures, five?M. bovis?were isolated and underwent WGS. All sequenced strains belonged to?Mycobacterium tuberculosis var bovis, spoligotype BOV_1; BOV_11. Resistance gene mutations were determined in 100% of strains to pyrazinamide (pncA?and?rpsA), isoniazid (KatG?and?ahpC), ethambutol (embB,?embC,?embR?and?ubiA), streptomycin (rpsl) and fluoroquinolones (gyrA?and?gyrB). Rifampin (rpoB?and?rpoC) and delamanid (fbiC) resistance genes were found in 80% of strains. The major represented virulence classes were the secretion system, cell surface components and regulation system.

Rifampin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: HIV-infected patients with tuberculosis [ICD-11: 1C60.0] [3]

• Resistant Disease: HIV-infected patients with tuberculosis [ICD-11: 1C60.0]
• Resistant Drug: Rifampin
• Molecule Alteration: Missense mutation; p.M306I
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Mycobacterium tuberculosis isolates; 1773
• Experiment for Molecule Alteration: DNA sequencing assay
• Experiment for Drug Resistance: Test for drug susceptibility in L-J medium assay
• Mechanism Description: An embB mutation has a strong relationship to rifampin resistance. Inhibition of cell wall biosynthesis may not play an important role, and inhibition of RNA metabolism may be partly responsible.

References

• Ref 1: Mycobacterial ethambutol responsive genes and implications in antibiotics resistance .J Drug Target. 2021 Mar;29(3):284-293. doi: 10.1080/1061186X.2020.1853733. Epub 2020 Dec 3. 10.1080/1061186X.2020.1853733
• Ref 2: Genetic diversities and drug resistance in Mycobacterium bovis isolates from zoonotic tuberculosis using whole genome sequencing. BMC Genomics. 2024 Nov 1;25(1):1024.
• Ref 3: Lack of correlation between embB mutation and ethambutol MIC in Mycobacterium tuberculosis clinical isolates from China. Antimicrob Agents Chemother. 2007 Dec;51(12):4515-7. doi: 10.1128/AAC.00416-07. Epub 2007 Sep 10.