Target Information
| Target General Information | Top | |||||
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| Target ID |
T24634
(Former ID: TTDS00233)
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| Target Name |
Bacterial UDP-N-acetylglucosamine carboxyvinyltransferase (Bact murA)
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| Synonyms |
UDP-N-acetylglucosamine enolpyruvyl transferase; UDP-GlcNAcenolpyruvyl transferase; MurA protein; MurA; Enoylpyruvate transferase; EPT
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| Gene Name |
Bact murA
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| Target Type |
Successful target
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[1] | ||||
| Disease | [+] 1 Target-related Diseases | + | ||||
| 1 | Bacterial infection [ICD-11: 1A00-1C4Z] | |||||
| Function |
Cell wall formation. Adds enolpyruvyl to UDP-n- acetylglucosamine. Target for the antibiotic phosphomycin.
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| BioChemical Class |
Alkyl aryl transferase
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| UniProt ID | ||||||
| Sequence |
MDKFRVQGPTKLQGEVTISGAKNAALPILFAALLAEEPVEIQNVPKLKDVDTSMKLLSQL
GAKVERNGSVHIDARDVNVFCAPYDLVKTMRASIWALGPLVARFGQGQVSLPGGCTIGAR PVDLHISGLEQLGATIKLEEGYVKASVDGRLKGAHIVMDKVSVGATVTIMCAATLAEGTT IIENAAREPEIVDTANFLITLGAKISGQGTDRIVIEGVERLGGGVYRVLPDRIETGTFLV AAAISRGKIICRNAQPDTLDAVLAKLRDAGADIEVGEDWISLDMHGKRPKAVNVRTAPHP AFPTDMQAQFTLLNLVAEGTGFITETVFENRFMHVPELSRMGAHAEIESNTVICHGVEKL SGAQVMATDLRASASLVLAGCIAEGTTVVDRIYHIDRGYERIEDKLRALGANIERVKGE Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | PDB | ||||
| HIT2.0 ID | T72T0K | |||||
| Drugs and Modes of Action | Top | |||||
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| Approved Drug(s) | [+] 1 Approved Drugs | + | ||||
| 1 | Fosfomycin | Drug Info | Approved | Bacterial infection | [2] | |
| Mode of Action | [+] 1 Modes of Action | + | ||||
| Inhibitor | [+] 10 Inhibitor drugs | + | ||||
| 1 | Fosfomycin | Drug Info | [1], [3], [4], [5] | |||
| 2 | Aminomethylcyclohexane | Drug Info | [6] | |||
| 3 | CNICIN | Drug Info | [7] | |||
| 4 | Cyclohexylammonium Ion | Drug Info | [6] | |||
| 5 | CYNAROPICRIN | Drug Info | [7] | |||
| 6 | EUPATORIOPICRIN | Drug Info | [7] | |||
| 7 | L-Iso-Aspartate | Drug Info | [6] | |||
| 8 | RWJ-140998 | Drug Info | [8] | |||
| 9 | RWJ-3981 | Drug Info | [8] | |||
| 10 | Uridine-Diphosphate-N-Acetylglucosamine | Drug Info | [9] | |||
| Drug Binding Sites of Target | Top | |||||
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| Ligand Name: L-aspartic acid | Ligand Info | |||||
| Structure Description | MurA binary complex with UDP-N-acetylglucosamine | PDB:3KQJ | ||||
| Method | X-ray diffraction | Resolution | 1.70 Å | Mutation | No | [10] |
| PDB Sequence |
MDKFRVQGPT
10 KLQGEVTISG20 AKNAALPILF30 AALLAEEPVE40 IQNVPKLKDV50 DTSMKLLSQL 60 GAKVERGSVH71 IDARDVNVFC81 APYDLVKTMR91 ASIWALGPLV101 ARFGQGQVSL 111 PGGCTIGARP121 VDLHISGLEQ131 LGATIKLEEG141 YVKASVDGRL151 KGAHIVMDKV 161 SVGATVTIMC171 AATLAEGTTI181 IENAAREPEI191 VDTANFLITL201 GAKISGQGTD 211 RIVIEGVERL221 GGGVYRVLPD231 RIETGTFLVA241 AAISRGKIIC251 RNAQPDTLDA 261 VLAKLRDAGA271 DIEVGEDWIS281 LDMHGKRPKA291 VNVRTAPHPA301 FPTDMQAQFT 311 LLNLVAEGTG321 FITETVFENR331 FMHVPELSRM341 GAHAEIESNT351 VICHGVEKLS 361 GAQVMATDLR371 ASASLVLAGC381 IAEGTTVVDR391 IYHIDRGYER401 IEDKLRALGA 411 NIERVKGE
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| Click to View More Binding Site Information of This Target and Ligand Pair | ||||||
| Ligand Name: Uridine-Diphosphate-N-Acetylglucosamine | Ligand Info | |||||
| Structure Description | MurA binary complex with UDP-N-acetylglucosamine | PDB:3KQJ | ||||
| Method | X-ray diffraction | Resolution | 1.70 Å | Mutation | No | [10] |
| PDB Sequence |
MDKFRVQGPT
10 KLQGEVTISG20 AKNAALPILF30 AALLAEEPVE40 IQNVPKLKDV50 DTSMKLLSQL 60 GAKVERGSVH71 IDARDVNVFC81 APYDLVKTMR91 ASIWALGPLV101 ARFGQGQVSL 111 PGGCTIGARP121 VDLHISGLEQ131 LGATIKLEEG141 YVKASVDGRL151 KGAHIVMDKV 161 SVGATVTIMC171 AATLAEGTTI181 IENAAREPEI191 VDTANFLITL201 GAKISGQGTD 211 RIVIEGVERL221 GGGVYRVLPD231 RIETGTFLVA241 AAISRGKIIC251 RNAQPDTLDA 261 VLAKLRDAGA271 DIEVGEDWIS281 LDMHGKRPKA291 VNVRTAPHPA301 FPTDMQAQFT 311 LLNLVAEGTG321 FITETVFENR331 FMHVPELSRM341 GAHAEIESNT351 VICHGVEKLS 361 GAQVMATDLR371 ASASLVLAGC381 IAEGTTVVDR391 IYHIDRGYER401 IEDKLRALGA 411 NIERVKGE
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LYS22
3.690
ASN23
3.160
LEU26
4.362
ARG91
2.928
ALA92
4.467
TRP95
3.354
ARG120
3.014
PRO121
3.175
VAL122
3.117
ASP123
2.807
LEU124
2.826
HIS125
3.523
LYS160
3.170
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| Click to View More Binding Site Information of This Target and Ligand Pair | ||||||
| Click to View More Binding Site Information of This Target with Different Ligands | ||||||
| Different Human System Profiles of Target | Top |
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Human Similarity Proteins
of target is determined by comparing the sequence similarity of all human proteins with the target based on BLAST. The similarity proteins for a target are defined as the proteins with E-value < 0.005 and outside the protein families of the target.
A target that has fewer human similarity proteins outside its family is commonly regarded to possess a greater capacity to avoid undesired interactions and thus increase the possibility of finding successful drugs
(Brief Bioinform, 21: 649-662, 2020).
Human Similarity Proteins
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There is no similarity protein (E value < 0.005) for this target
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| Chemical Structure based Activity Landscape of Target | Top |
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| Drug Property Profile of Target | Top | |
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| (1) Molecular Weight (mw) based Drug Clustering | (2) Octanol/Water Partition Coefficient (xlogp) based Drug Clustering | |
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| (3) Hydrogen Bond Donor Count (hbonddonor) based Drug Clustering | (4) Hydrogen Bond Acceptor Count (hbondacc) based Drug Clustering | |
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| (5) Rotatable Bond Count (rotbonds) based Drug Clustering | (6) Topological Polar Surface Area (polararea) based Drug Clustering | |
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| "RO5" indicates the cutoff set by lipinski's rule of five; "D123AB" colored in GREEN denotes the no violation of any cutoff in lipinski's rule of five; "D123AB" colored in PURPLE refers to the violation of only one cutoff in lipinski's rule of five; "D123AB" colored in BLACK represents the violation of more than one cutoffs in lipinski's rule of five | ||
| Target Poor or Non Binders | Top | |||||
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| Target Poor or Non Binders | ||||||
| Target Profiles in Patients | Top | |||||
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| Drug Resistance Mutation (DRM) | ||||||
| Target-Related Models and Studies | Top | |||||
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| Target Validation | ||||||
| References | Top | |||||
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| REF 1 | Evidence that the fosfomycin target Cys115 in UDP-N-acetylglucosamine enolpyruvyl transferase (MurA) is essential for product release. J Biol Chem. 2005 Feb 4;280(5):3757-63. | |||||
| REF 2 | Has nature already identified all useful antibacterial targets Curr Opin Microbiol. 2008 Oct;11(5):387-92. | |||||
| REF 3 | Conditional lethal amber mutations in essential Escherichia coli genes. J Bacteriol. 2004 May;186(9):2673-81. | |||||
| REF 4 | In vitro and in vivo functional activity of Chlamydia MurA, a UDP-N-acetylglucosamine enolpyruvyl transferase involved in peptidoglycan synthesis and fosfomycin resistance. J Bacteriol. 2003 Feb;185(4):1218-28. | |||||
| REF 5 | Lysine 22 in UDP-N-acetylglucosamine enolpyruvyl transferase from Enterobacter cloacae is crucial for enzymatic activity and the formation of covalent adducts with the substrate phosphoenolpyruvate and the antibiotic fosfomycin. Biochemistry. 1999 Oct 5;38(40):13162-9. | |||||
| REF 6 | How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6. | |||||
| REF 7 | Sesquiterpene lactones are potent and irreversible inhibitors of the antibacterial target enzyme MurA. Bioorg Med Chem Lett. 2006 Nov 1;16(21):5605-9. | |||||
| REF 8 | Emerging drugs for bacterial urinary tract infections. Expert Opin Emerg Drugs. 2005 May;10(2):275-98. | |||||
| REF 9 | DrugBank 3.0: a comprehensive resource for 'omics' research on drugs. Nucleic Acids Res. 2011 Jan;39(Database issue):D1035-41. | |||||
| REF 10 | MurA binary complex with UDP-N-acetylglucosamine | |||||
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