Drug Information

Drug (ID: DG00381) and It's Reported Resistant Information

• Name: Enacyloxin IIA
• Synonyms: Enacyloxin iia; Q27459995; (1S,3R,4S)-3-{[(2E,4E,6E,8E,10Z,12S,13R,14S,17R,18S,19R,20E)-19-(carbamoyloxy)-11,18-dichloro-13,14,17-trihydroxy-6,12-dimethyl-15-oxotricosa-2,4,6,8,10,20-hexaenoyl]oxy}-4-hydroxycyclohexanecarboxylic acid
• 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: C33H45Cl2NO11
• IsoSMILES: CC/C=C/[C@H]([C@H]([C@@H](CC(=O)[C@H]([C@@H]([C@H](C)/C(=C/C=C/C=C(\\C)/C=C/C=C/C(=O)O[C@@H]1C[C@H](CC[C@@H]1O)C(=O)O)/Cl)O)O)O)Cl)OC(=O)N
• InChI: 1S/C33H45Cl2NO11/c1-4-5-13-26(47-33(36)45)29(35)24(38)18-25(39)31(42)30(41)20(3)22(34)12-8-6-10-19(2)11-7-9-14-28(40)46-27-17-21(32(43)44)15-16-23(27)37/h5-14,20-21,23-24,26-27,29-31,37-38,41-42H,4,15-18H2,1-3H3,(H2,36,45)(H,43,44)/b8-6+,11-7+,13-5+,14-9+,19-10+,22-12-/t20-,21+,23+,24-,26-,27-,29+,30-,31-/m1/s1
• InChIKey: IWBADCVFZDCUTN-OCXJTLLTSA-N
• PubChem CID: 5288163

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: Outer membrane porin F (OMPF) [1]

• Molecule Alteration: Missense mutation; p.Q124K
• Resistant Disease: Escherichia coli infection [ICD-11: 1A03.0]
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Escherichia coli strain LZ10; 562
• In Vitro Model: Escherichia coli strain LZ33L; 562
• In Vitro Model: Escherichia coli strain EV4; 562
• In Vitro Model: Escherichia coli strain EV4L; 562
• In Vitro Model: Escherichia coli strain LZ12; 562
• In Vitro Model: Escherichia coli strain LZ13; 562
• In Vitro Model: Escherichia coli strain LZ32; 562
• In Vitro Model: Escherichia coli strain LZ34L; 562
• In Vitro Model: Escherichia coli strain LZ40L; 562
• In Vitro Model: Escherichia coli strain PM816; 562
• Experiment for Molecule Alteration: PCR
• Experiment for Drug Resistance: MIC assay
• Mechanism Description: For enacyloxin IIa we discovered four resistant elongation factor Tu (EF-Tu) species in Escherichia coli with the mutations Q124k, G316D, Q329H, and A375T. Among the mutant EF-Tus, three different resistance mechanisms can be distinguished: (i) by obstructing enacyloxin IIa binding to EF-Tu. GTP; (ii) by enabling the release of enacyloxin IIa after GTP hydrolysis; and (iii) by reducing the affinity of EF-Tu.GDP. enacyloxin IIa for aminoacyl-tRNA at the ribosomal A-site, which then allows the release of EF-Tu.GDP.enacyloxin IIa. Ala375 seems to contribute directly to enacyloxin IIa binding at the domain 1-3 interface of EF-Tu.GTP, a location that would easily explain the pleiotropic effects of enacyloxin IIa on the functioning of EF-Tu.

Key Molecule: Outer membrane porin F (OMPF) [1]

• Molecule Alteration: Missense mutation; p.G316D
• Resistant Disease: Escherichia coli infection [ICD-11: 1A03.0]
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Escherichia coli strain LZ10; 562
• In Vitro Model: Escherichia coli strain LZ33L; 562
• In Vitro Model: Escherichia coli strain EV4; 562
• In Vitro Model: Escherichia coli strain EV4L; 562
• In Vitro Model: Escherichia coli strain LZ12; 562
• In Vitro Model: Escherichia coli strain LZ13; 562
• In Vitro Model: Escherichia coli strain LZ32; 562
• In Vitro Model: Escherichia coli strain LZ34L; 562
• In Vitro Model: Escherichia coli strain LZ40L; 562
• In Vitro Model: Escherichia coli strain PM816; 562
• Experiment for Molecule Alteration: PCR
• Experiment for Drug Resistance: MIC assay
• Mechanism Description: For enacyloxin IIa we discovered four resistant elongation factor Tu (EF-Tu) species in Escherichia coli with the mutations Q124k, G316D, Q329H, and A375T. Among the mutant EF-Tus, three different resistance mechanisms can be distinguished: (i) by obstructing enacyloxin IIa binding to EF-Tu. GTP; (ii) by enabling the release of enacyloxin IIa after GTP hydrolysis; and (iii) by reducing the affinity of EF-Tu.GDP. enacyloxin IIa for aminoacyl-tRNA at the ribosomal A-site, which then allows the release of EF-Tu.GDP.enacyloxin IIa. Ala375 seems to contribute directly to enacyloxin IIa binding at the domain 1-3 interface of EF-Tu.GTP, a location that would easily explain the pleiotropic effects of enacyloxin IIa on the functioning of EF-Tu.

Key Molecule: Outer membrane porin F (OMPF) [1]

• Molecule Alteration: Missense mutation; p.Q329H
• Resistant Disease: Escherichia coli infection [ICD-11: 1A03.0]
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Escherichia coli strain LZ10; 562
• In Vitro Model: Escherichia coli strain LZ33L; 562
• In Vitro Model: Escherichia coli strain EV4; 562
• In Vitro Model: Escherichia coli strain EV4L; 562
• In Vitro Model: Escherichia coli strain LZ12; 562
• In Vitro Model: Escherichia coli strain LZ13; 562
• In Vitro Model: Escherichia coli strain LZ32; 562
• In Vitro Model: Escherichia coli strain LZ34L; 562
• In Vitro Model: Escherichia coli strain LZ40L; 562
• In Vitro Model: Escherichia coli strain PM816; 562
• Experiment for Molecule Alteration: PCR
• Experiment for Drug Resistance: MIC assay
• Mechanism Description: For enacyloxin IIa we discovered four resistant elongation factor Tu (EF-Tu) species in Escherichia coli with the mutations Q124k, G316D, Q329H, and A375T. Among the mutant EF-Tus, three different resistance mechanisms can be distinguished: (i) by obstructing enacyloxin IIa binding to EF-Tu. GTP; (ii) by enabling the release of enacyloxin IIa after GTP hydrolysis; and (iii) by reducing the affinity of EF-Tu.GDP. enacyloxin IIa for aminoacyl-tRNA at the ribosomal A-site, which then allows the release of EF-Tu.GDP.enacyloxin IIa. Ala375 seems to contribute directly to enacyloxin IIa binding at the domain 1-3 interface of EF-Tu.GTP, a location that would easily explain the pleiotropic effects of enacyloxin IIa on the functioning of EF-Tu.

Key Molecule: Outer membrane porin F (OMPF) [1]

• Molecule Alteration: Missense mutation; p.A375T
• Resistant Disease: Escherichia coli infection [ICD-11: 1A03.0]
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Escherichia coli strain LZ10; 562
• In Vitro Model: Escherichia coli strain LZ33L; 562
• In Vitro Model: Escherichia coli strain EV4; 562
• In Vitro Model: Escherichia coli strain EV4L; 562
• In Vitro Model: Escherichia coli strain LZ12; 562
• In Vitro Model: Escherichia coli strain LZ13; 562
• In Vitro Model: Escherichia coli strain LZ32; 562
• In Vitro Model: Escherichia coli strain LZ34L; 562
• In Vitro Model: Escherichia coli strain LZ40L; 562
• In Vitro Model: Escherichia coli strain PM816; 562
• Experiment for Molecule Alteration: PCR
• Experiment for Drug Resistance: MIC assay
• Mechanism Description: For enacyloxin IIa we discovered four resistant elongation factor Tu (EF-Tu) species in Escherichia coli with the mutations Q124k, G316D, Q329H, and A375T. Among the mutant EF-Tus, three different resistance mechanisms can be distinguished: (i) by obstructing enacyloxin IIa binding to EF-Tu. GTP; (ii) by enabling the release of enacyloxin IIa after GTP hydrolysis; and (iii) by reducing the affinity of EF-Tu.GDP. enacyloxin IIa for aminoacyl-tRNA at the ribosomal A-site, which then allows the release of EF-Tu.GDP.enacyloxin IIa. Ala375 seems to contribute directly to enacyloxin IIa binding at the domain 1-3 interface of EF-Tu.GTP, a location that would easily explain the pleiotropic effects of enacyloxin IIa on the functioning of EF-Tu.

References

• Ref 1: Mutant EF-Tu species reveal novel features of the enacyloxin IIa inhibition mechanism on the ribosome. J Mol Biol. 1999 Dec 3;294(3):627-37. doi: 10.1006/jmbi.1999.3296.