Target Information
| Target General Information | Top | |||||
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| Target ID |
T72444
(Former ID: TTDR00361)
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| Target Name |
Bacterial Beta-ketoacyl-ACP synthase III (Bact fabH)
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| Synonyms |
KAS III; FabH; EcFabH; Condensing enzyme FabH; Beta-ketoacyl-acyl carrier protein synthase III; Acetoacetyl-acyl carrier protein synthase; Acetoacetyl-ACP synthase; 3-oxoacyl-[acyl-carrier-protein] synthase III
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| Gene Name |
Bact fabH
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| Target Type |
Literature-reported target
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[1] | ||||
| Disease | [+] 2 Target-related Diseases | + | ||||
| 1 | Malaria [ICD-11: 1F40-1F45] | |||||
| 2 | Urinary tract infection [ICD-11: GC08] | |||||
| Function |
Catalyzes the condensation reaction of fatty acid synthesis by the addition to an acyl acceptor of two carbons from malonyl-ACP. Catalyzes the first condensation reaction which initiates fatty acid synthesis and may therefore play a role in governing the total rate of fatty acid production. Possesses both acetoacetyl-ACP synthase and acetyl transacylase activities. Has some substrate specificity for acetyl-CoA. Its substrate specificity determines the biosynthesis of straight-chain of fatty acids instead of branched-chain.
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| BioChemical Class |
Acyltransferase
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| UniProt ID | ||||||
| EC Number |
EC 2.3.1.180
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| Sequence |
MYTKIIGTGSYLPEQVRTNADLEKMVDTSDEWIVTRTGIRERHIAAPNETVSTMGFEAAT
RAIEMAGIEKDQIGLIVVATTSATHAFPSAACQIQSMLGIKGCPAFDVAAACAGFTYALS VADQYVKSGAVKYALVVGSDVLARTCDPTDRGTIIIFGDGAGAAVLAASEEPGIISTHLH ADGSYGELLTLPNADRVNPENSIHLTMAGNEVFKVAVTELAHIVDETLAANNLDRSQLDW LVPHQANLRIISATAKKLGMSMDNVVVTLDRHGNTSAASVPCALDEAVRDGRIKPGQLVL LEAFGGGFTWGSALVRF 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: Malonyl-CoA | Ligand Info | |||||
| Structure Description | CRYSTAL STRUCTURE OF BETA-KETOACYL-ACP SYNTHASE III + MALONYL-COA | PDB:1HNJ | ||||
| Method | X-ray diffraction | Resolution | 1.46 Å | Mutation | No | [4] |
| PDB Sequence |
MYTKIIGTGS
10 YLPEQVRTNA20 DLEKMVDTSD30 EWIVTRTGIR40 ERHIAAPNET50 VSTMGFEAAT 60 RAIEMAGIEK70 DQIGLIVVAT80 TSATHAFPSA90 ACQIQSMLGI100 KGCPAFDVAA 110 ACAGFTYALS120 VADQYVKSGA130 VKYALVVGSD140 VLARTCDPTD150 RGTIIIFGDG 160 AGAAVLAASE170 EPGIISTHLH180 ADGSYGELLT190 LPNADRVNPE200 NSIHLTMAGN 210 EVFKVAVTEL220 AHIVDETLAA230 NNLDRSQLDW240 LVPHQANLRI250 ISATAKKLGM 260 SMDNVVVTLD270 RHGNTSAASV280 PCALDEAVRD290 GRIKPGQLVL300 LEAFGGGFTW 310 GSALVRF
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ASP27
3.819
THR28
2.625
SER29
4.628
TRP32
3.256
ILE33
4.915
ARG36
2.990
THR37
3.448
CYS112
4.505
ARG151
2.931
GLY152
3.794
ILE155
3.559
ILE156
3.764
LEU189
3.786
MET207
3.541
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| Ligand Name: Coenzyme A | Ligand Info | |||||
| Structure Description | CRYSTAL STRUCTURE OF BETA-KETOACYL-ACP SYNTHASE III-COA COMPLEX | PDB:1HND | ||||
| Method | X-ray diffraction | Resolution | 1.60 Å | Mutation | No | [4] |
| PDB Sequence |
MYTKIIGTGS
10 YLPEQVRTNA20 DLEKMVDTSD30 EWIVTRTGIR40 ERHIAAPNET50 VSTMGFEAAT 60 RAIEMAGIEK70 DQIGLIVVAT80 TSATHAFPSA90 ACQIQSMLGI100 KGCPAFDVAA 110 ACAGFTYALS120 VADQYVKSGA130 VKYALVVGSD140 VLARTCDPTD150 RGTIIIFGDG 160 AGAAVLAASE170 EPGIISTHLH180 ADGSYGELLT190 LPNADRVNPE200 NSIHLTMAGN 210 EVFKVAVTEL220 AHIVDETLAA230 NNLDRSQLDW240 LVPHQANLRI250 ISATAKKLGM 260 SMDNVVVTLD270 RHGNTSAASV280 PCALDEAVRD290 GRIKPGQLVL300 LEAFGGGFTW 310 GSALVRF
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ASP27
3.811
THR28
2.593
SER29
4.600
TRP32
3.232
ILE33
4.752
ARG36
3.294
THR37
3.569
CYS112
2.838
ARG151
2.930
GLY152
3.821
ILE155
3.410
ILE156
3.389
LEU189
3.419
MET207
3.559
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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-Related Models and Studies | Top | |||||
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| Target Validation | ||||||
| Target QSAR Model | ||||||
| References | Top | |||||
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| REF 1 | The apicoplast as an antimalarial drug target. Drug Resist Updat. 2001 Jun;4(3):145-51. | |||||
| REF 2 | Structure-based design, synthesis, and study of potent inhibitors of beta-ketoacyl-acyl carrier protein synthase III as potential antimicrobial age... J Med Chem. 2005 Mar 10;48(5):1596-609. | |||||
| REF 3 | Synthesis and biological evaluation of novel sulfonyl-naphthalene-1,4-diols as FabH inhibitors. Bioorg Med Chem Lett. 2008 Dec 15;18(24):6402-5. | |||||
| REF 4 | Refined structures of beta-ketoacyl-acyl carrier protein synthase III. J Mol Biol. 2001 Mar 16;307(1):341-56. | |||||
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