Drug Information

Drug (ID: DG00009) and It's Reported Resistant Information

• Name: Pulvomycin
• Synonyms: Pulvomycin; AC1NQZFA; C12070; 11006-66-9; CHEBI:29668
• Indication:
  In total 1 Indication(s)
  Bacterial infection [ICD-11: 1A00-1C4Z]; Investigative; [1]
• Drug Resistance Disease(s):
  Disease(s) with Resistance Information Validated by in-vivo Model for This Drug (1 diseases)
  Escherichia coli intestinal infection [ICD-11: 1A03]; [1]
• Formula: C47H66O13
• IsoSMILES: C[C@@H]1[C@@H]([C@@H]([C@H]([C@@H](O1)OC(C)C(/C=C/C=C/C=C/C(=O)C(C)C(C(C)C2C/C=C/C=C/C=C/C(C(=O)/C(=C/C=C/C(=C/C(/C(=C\\CC(=O)O2)/C)O)/C)/C)O)O)O)OC)O)OC
• InChI: 1S/C47H66O13/c1-29-20-19-21-31(3)42(53)38(50)24-17-11-10-12-18-25-40(60-41(52)27-26-30(2)39(51)28-29)33(5)43(54)32(4)36(48)22-15-13-14-16-23-37(49)34(6)58-47-46(57-9)44(55)45(56-8)35(7)59-47/h10-24,26,28,32-35,37-40,43-47,49-51,54-55H,25,27H2,1-9H3/b11-10+,14-13+,18-12+,20-19+,22-15+,23-16+,24-17+,29-28+,30-26-,31-21+/t32 ,33 ,34 ,35-,37 ,38 ,39 ,40 ,43 ,44+,45+,46-,47-/m1/s1
• InChIKey: FXSFWUNCIOIMAC-YHQXOMPPSA-N
• PubChem CID: 5282056
• ChEBI ID: CHEBI:29668
• TTD Drug ID: D00YCO

Type(s) of Resistant Mechanism of This Drug

  ADTT: Aberration of the Drug's Therapeutic Target

Drug Resistance Data Categorized by Their Corresponding Diseases

ICD-01: Infectious/parasitic diseases

Escherichia coli intestinal infection [ICD-11: 1A03]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Elongation factor Tu 1 (TUFA) [1]

• Molecule Alteration: Missense mutation; p.R230C
• Resistant Disease: Escherichia coli infection [ICD-11: 1A03.0]
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Escherichia coli strain LZ33L; 562
• In Vitro Model: Escherichiacoli strain EV4; 562
• In Vitro Model: Escherichiacoli strain LBE2040; 562
• In Vitro Model: Escherichiacoli strain LZ32L; 562
• In Vitro Model: Escherichiacoli strain LZ35L; 562
• In Vitro Model: Escherichiacoli strain LZ36L; 562
• In Vitro Model: Escherichiacoli strain LZ37L; 562
• In Vitro Model: Escherichiacoli strain MG1655; 511145
• Experiment for Drug Resistance: MIC assay
• Mechanism Description: Together with targeted mutagenesis of the tufA gene, conditions were found to overcome membrane impermeability, thereby allowing the selection of three mutants harbouring elongation factor (EF)-Tu Arg230-->Cys, Arg333-->Cys or Thr334-->Ala which confer pulvomycin resistance.Pulvomycin and kirromycin both act by specifically disturbing the allosteric changes required for the switch from EF-Tu-GTP to EF-Tu-GDP. The three-domain junction changes dramatically in the switch to EF-Tu.GDP; in EF-Tu.GDP this region forms an open hole. The two most highly resistant mutants, R230C and R333C, are part of an electrostatic network involving numerous residues.

Key Molecule: Elongation factor Tu 2 (TUFB) [1]

• Molecule Alteration: Missense mutation; p.R230C
• Resistant Disease: Escherichia coli infection [ICD-11: 1A03.0]
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Escherichia coli strain LZ33L; 562
• In Vitro Model: Escherichiacoli strain EV4; 562
• In Vitro Model: Escherichiacoli strain LBE2040; 562
• In Vitro Model: Escherichiacoli strain LZ32L; 562
• In Vitro Model: Escherichiacoli strain LZ35L; 562
• In Vitro Model: Escherichiacoli strain LZ36L; 562
• In Vitro Model: Escherichiacoli strain LZ37L; 562
• In Vitro Model: Escherichiacoli strain MG1655; 511145
• Experiment for Drug Resistance: MIC assay
• Mechanism Description: Together with targeted mutagenesis of the tufA gene, conditions were found to overcome membrane impermeability, thereby allowing the selection of three mutants harbouring elongation factor (EF)-Tu Arg230-->Cys, Arg333-->Cys or Thr334-->Ala which confer pulvomycin resistance.Pulvomycin and kirromycin both act by specifically disturbing the allosteric changes required for the switch from EF-Tu-GTP to EF-Tu-GDP. The three-domain junction changes dramatically in the switch to EF-Tu.GDP; in EF-Tu.GDP this region forms an open hole. The two most highly resistant mutants, R230C and R333C, are part of an electrostatic network involving numerous residues.

Key Molecule: Elongation factor Tu 1 (TUFA) [1]

• Molecule Alteration: Missense mutation; p.R333C
• Resistant Disease: Escherichia coli infection [ICD-11: 1A03.0]
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Escherichia coli strain LZ33L; 562
• In Vitro Model: Escherichiacoli strain EV4; 562
• In Vitro Model: Escherichiacoli strain LBE2040; 562
• In Vitro Model: Escherichiacoli strain LZ32L; 562
• In Vitro Model: Escherichiacoli strain LZ35L; 562
• In Vitro Model: Escherichiacoli strain LZ36L; 562
• In Vitro Model: Escherichiacoli strain LZ37L; 562
• In Vitro Model: Escherichiacoli strain MG1655; 511145
• Experiment for Drug Resistance: MIC assay
• Mechanism Description: Together with targeted mutagenesis of the tufA gene, conditions were found to overcome membrane impermeability, thereby allowing the selection of three mutants harbouring elongation factor (EF)-Tu Arg230-->Cys, Arg333-->Cys or Thr334-->Ala which confer pulvomycin resistance.Pulvomycin and kirromycin both act by specifically disturbing the allosteric changes required for the switch from EF-Tu-GTP to EF-Tu-GDP. The three-domain junction changes dramatically in the switch to EF-Tu.GDP; in EF-Tu.GDP this region forms an open hole. The two most highly resistant mutants, R230C and R333C, are part of an electrostatic network involving numerous residues.

Key Molecule: Elongation factor Tu 2 (TUFB) [1]

• Molecule Alteration: Missense mutation; p.R333C
• Resistant Disease: Escherichia coli infection [ICD-11: 1A03.0]
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Escherichia coli strain LZ33L; 562
• In Vitro Model: Escherichiacoli strain EV4; 562
• In Vitro Model: Escherichiacoli strain LBE2040; 562
• In Vitro Model: Escherichiacoli strain LZ32L; 562
• In Vitro Model: Escherichiacoli strain LZ35L; 562
• In Vitro Model: Escherichiacoli strain LZ36L; 562
• In Vitro Model: Escherichiacoli strain LZ37L; 562
• In Vitro Model: Escherichiacoli strain MG1655; 511145
• Experiment for Drug Resistance: MIC assay
• Mechanism Description: Together with targeted mutagenesis of the tufA gene, conditions were found to overcome membrane impermeability, thereby allowing the selection of three mutants harbouring elongation factor (EF)-Tu Arg230-->Cys, Arg333-->Cys or Thr334-->Ala which confer pulvomycin resistance.Pulvomycin and kirromycin both act by specifically disturbing the allosteric changes required for the switch from EF-Tu-GTP to EF-Tu-GDP. The three-domain junction changes dramatically in the switch to EF-Tu.GDP; in EF-Tu.GDP this region forms an open hole. The two most highly resistant mutants, R230C and R333C, are part of an electrostatic network involving numerous residues.

Key Molecule: Elongation factor Tu 1 (TUFA) [1]

• Molecule Alteration: Missense mutation; p.T334A
• Resistant Disease: Escherichia coli infection [ICD-11: 1A03.0]
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Escherichia coli strain LZ33L; 562
• In Vitro Model: Escherichiacoli strain EV4; 562
• In Vitro Model: Escherichiacoli strain LBE2040; 562
• In Vitro Model: Escherichiacoli strain LZ32L; 562
• In Vitro Model: Escherichiacoli strain LZ35L; 562
• In Vitro Model: Escherichiacoli strain LZ36L; 562
• In Vitro Model: Escherichiacoli strain LZ37L; 562
• In Vitro Model: Escherichiacoli strain MG1655; 511145
• Experiment for Drug Resistance: MIC assay
• Mechanism Description: Together with targeted mutagenesis of the tufA gene, conditions were found to overcome membrane impermeability, thereby allowing the selection of three mutants harbouring elongation factor (EF)-Tu Arg230-->Cys, Arg333-->Cys or Thr334-->Ala which confer pulvomycin resistance.Pulvomycin and kirromycin both act by specifically disturbing the allosteric changes required for the switch from EF-Tu-GTP to EF-Tu-GDP. The three-domain junction changes dramatically in the switch to EF-Tu.GDP; in EF-Tu.GDP this region forms an open hole. The two most highly resistant mutants, R230C and R333C, are part of an electrostatic network involving numerous residues.

Key Molecule: Elongation factor Tu 2 (TUFB) [1]

• Molecule Alteration: Missense mutation; p.T334A
• Resistant Disease: Escherichia coli infection [ICD-11: 1A03.0]
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Escherichia coli strain LZ33L; 562
• In Vitro Model: Escherichiacoli strain EV4; 562
• In Vitro Model: Escherichiacoli strain LBE2040; 562
• In Vitro Model: Escherichiacoli strain LZ32L; 562
• In Vitro Model: Escherichiacoli strain LZ35L; 562
• In Vitro Model: Escherichiacoli strain LZ36L; 562
• In Vitro Model: Escherichiacoli strain LZ37L; 562
• In Vitro Model: Escherichiacoli strain MG1655; 511145
• Experiment for Drug Resistance: MIC assay
• Mechanism Description: Together with targeted mutagenesis of the tufA gene, conditions were found to overcome membrane impermeability, thereby allowing the selection of three mutants harbouring elongation factor (EF)-Tu Arg230-->Cys, Arg333-->Cys or Thr334-->Ala which confer pulvomycin resistance.Pulvomycin and kirromycin both act by specifically disturbing the allosteric changes required for the switch from EF-Tu-GTP to EF-Tu-GDP. The three-domain junction changes dramatically in the switch to EF-Tu.GDP; in EF-Tu.GDP this region forms an open hole. The two most highly resistant mutants, R230C and R333C, are part of an electrostatic network involving numerous residues.

References

• Ref 1: Pulvomycin-resistant mutants of E.coli elongation factor Tu. EMBO J. 1994 Nov 1;13(21):5113-20.