Target Information
| Target General Information | Top | |||||
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| Target ID |
T85944
(Former ID: TTDR00865)
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| Target Name |
Pseudomonas UDP-3-O-acyl-GlcNAc deacetylase (Pseudo lpxC)
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| Synonyms |
Pseudo UDP-3-O-acyl-GlcNAc deacetylase; EnvA protein
Click to Show/Hide
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| Gene Name |
Pseudo lpxC
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| Target Type |
Preclinical target
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[1] | ||||
| Disease | [+] 2 Target-related Diseases | + | ||||
| 1 | Pneumonia [ICD-11: CA40] | |||||
| 2 | Gram-negative bacterial infection [ICD-11: 1F41-1G40] | |||||
| Function |
Involved in the biosynthesis of lipid A, a phosphorylated glycolipid that anchors the lipopolysaccharide to the outer membrane of the cell.
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| BioChemical Class |
Carbon-nitrogen hydrolase
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| UniProt ID | ||||||
| EC Number |
EC 3.5.1.108
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| Sequence |
MIKQRTLKNIIRATGVGLHSGEKVYLTLKPAPVDTGIVFCRTDLDPVVEIPARAENVGET
TMSTTLVKGDVKVDTVEHLLSAMAGLGIDNAYVELSASEVPIMDGSAGPFVFLIQSAGLQ EQEAAKKFIRIKREVSVEEGDKRAVFVPFDGFKVSFEIDFDHPVFRGRTQQASVDFSSTS FVKEVSRARTFGFMRDIEYLRSQNLALGGSVENAIVVDENRVLNEDGLRYEDEFVKHKIL DAIGDLYLLGNSLIGEFRGFKSGHALNNQLLRTLIADKDAWEVVTFEDARTAPISYMRPA AAV Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | PDB | ||||
| Drug Binding Sites of Target | Top | |||||
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| Ligand Name: ACHN-975 | Ligand Info | |||||
| Structure Description | Co-Crystal structure of P. aeruginosa LpxC-achn975 complex | PDB:6MOO | ||||
| Method | X-ray diffraction | Resolution | 2.20 Å | Mutation | No | [6] |
| PDB Sequence |
HHEGAGTIKQ
4 RTLKNIIRAT14 GVGLHSGEKV24 YLTLKPAPVD34 TGIVFSRTDL44 DPVVEIPARA 54 ENVGETTMST64 TLVKGDVKVD74 TVEHLLSAMA84 GLGIDNAYVE94 LSASEVPIMD 104 GSAGPFVFLI114 QSAGLQEQEA124 AKKFIRIKRE134 VSVEEGDKRA144 VFVPFDGFKV 154 SFEIDFDHPV164 FQQASVDFSS178 TSFVKEVSRA188 RTFGFMRDIE198 YLRSQNLALG 208 GSVENAIVVD218 ENRVLNEDGL228 RYEDEFVKHK238 ILDAIGDLYL248 LGNSLIGEFR 258 GFKSGHALNN268 QLLRTLIADK278 DAWEVVTFED288 ARTAPISYMR298 P |
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LEU18
3.871
HIS19
4.225
MET62
4.010
SER63
4.948
GLU77
2.274
HIS78
3.119
THR190
2.308
PHE191
3.150
GLY192
4.088
MET194
4.006
ILE197
3.753
LEU200
4.533
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| Ligand Name: BB-78485 | Ligand Info | |||||
| Structure Description | Crystal Structure of LpxC from Pseudomonas aeruginosa complexed with the potent BB-78485 inhibitor | PDB:2VES | ||||
| Method | X-ray diffraction | Resolution | 1.90 Å | Mutation | No | [7] |
| PDB Sequence |
MIKQRTLKNI
10 IRATGVGLHS20 GEKVYLTLKP30 APVDTGIVFS40 RTDLDPVVEI50 PARAENVGET 60 TMSTTLVKGD70 VKVDTVEHLL80 SAMAGLGIDN90 AYVELSASEV100 PIMDGSAGPF 110 VFLIQSAGLQ120 EQEAAKKFIR130 IKREVSVEEG140 DKRAVFVPFD150 GFKVSFEIDF 160 DHPVFRGRTQ170 QASVDFSSTS180 FVKEVSRART190 FGFMRDIEYL200 RSQNLALGGS 210 VENAIVVDEN220 RVLNEDGLRY230 EDEFVKHKIL240 DAIGDLYLLG250 NSLIGEFRGF 260 KSGHALNNQL270 LRTLIADKDA280 WEVVTFEDAR290 TAPI
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LEU18
3.149
MET62
2.985
SER63
3.705
THR75
3.941
GLU77
2.512
HIS78
3.243
ILE102
3.846
THR190
2.672
PHE191
3.257
GLY192
3.456
PHE193
3.830
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| 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 Affiliated Biological Pathways | Top | |||||
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| KEGG Pathway | [+] 2 KEGG Pathways | + | ||||
| 1 | Lipopolysaccharide biosynthesis | |||||
| 2 | Metabolic pathways | |||||
| Target-Related Models and Studies | Top | |||||
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| Target QSAR Model | ||||||
| References | Top | |||||
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| REF 1 | How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6. | |||||
| REF 2 | Different drugs for bad bugs: antivirulence strategies in the age of antibiotic resistance. Nat Rev Drug Discov. 2017 Jul;16(7):457-471. | |||||
| REF 3 | The global preclinical antibacterial pipeline. Nat Rev Microbiol. 2020 May;18(5):275-285. | |||||
| REF 4 | The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. | |||||
| REF 5 | Antibacterial activities and characterization of novel inhibitors of LpxC. Antimicrob Agents Chemother. 2002 Jun;46(6):1793-9. | |||||
| REF 6 | Optimization of LpxC Inhibitors for Antibacterial Activity and Cardiovascular Safety. ChemMedChem. 2019 Aug 20;14(16):1560-1572. | |||||
| REF 7 | Crystal structure of LpxC from Pseudomonas aeruginosa complexed with the potent BB-78485 inhibitor. Protein Sci. 2008 Mar;17(3):450-7. | |||||
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