Target Information

Target General Information

Top

Target ID

T23036 (Former ID: TTDI02067)

Target Name

Staphylococcus Enoyl ACP reductase (Stap-coc fabI)

Synonyms

NADPHdependent enoylACP reductase; Enoyl[acylcarrierprotein] reductase [NADPH] FabI

Click to Show/Hide

Gene Name

Stap-coc fabI

Target Type

Clinical trial target

[1]

Disease

[+] 2 Target-related Diseases

Bacterial infection [ICD-11: 1A00-1C4Z]

Staphylococcal/streptococcal disease [ICD-11: 1B5Y]

Function

Catalyzes the reduction of a carbon-carbon double bond in an enoyl moiety that is covalently linked to an acyl carrier protein (ACP). It has a preference for a long chain (C12) substrate compared to the shorter (C4) acyl group. Involved in the elongation cycle of fatty acid which are used in the lipid metabolism.

Click to Show/Hide

BioChemical Class

Short-chain dehydrogenases reductase

UniProt ID

FABI_STAA8

Sequence

MLNLENKTYVIMGIANKRSIAFGVAKVLDQLGAKLVFTYRKERSRKELEKLLEQLNQPEA
HLYQIDVQSDEEVINGFEQIGKDVGNIDGVYHSIAFANMEDLRGRFSETSREGFLLAQDI
SSYSLTIVAHEAKKLMPEGGSIVATTYLGGEFAVQNYNVMGVAKASLEANVKYLALDLGP
DNIRVNAISASPIRTLSAKGVGGFNTILKEIEERAPLKRNVDQVEVGKTAAYLLSDLSSG
VTGENIHVDSGFHAIK

Click to Show/Hide

3D Structure

Click to Show 3D Structure of This Target

PDB

Drugs and Modes of Action

Top

Clinical Trial Drug(s)

[+] 3 Clinical Trial Drugs

Afabicin

Drug Info

Phase 2

Acute bacterial skin infection

[2]

AFN-1252

Drug Info

Phase 2

Staphylococcus infection

[3]

CG-400549

Drug Info

Phase 2

Bacterial infection

[4]

Preclinical Drug(s)

[+] 1 Preclinical Drugs

MUT-056399

Drug Info

Preclinical

Methicillin-resistant staphylococci infection

[5]

Mode of Action

[+] 2 Modes of Action

Inhibitor

[+] 3 Inhibitor drugs

Afabicin

Drug Info

[2]

AFN-1252

Drug Info

[3]

CG-400549

Drug Info

[1]

Modulator

[+] 1 Modulator drugs

MUT-056399

Drug Info

[6]

Drug Binding Sites of Target

Top

Ligand Name: NADP+

Ligand Info

Structure Description

Crystal structure of S. aureus FabI inhibited by SKTS1

PDB:6YUR

Method

X-ray diffraction

Resolution

1.96 Å

Mutation

[7]

PDB Sequence

VNLENKTYVI

¹¹

MGIANKRSIA

²¹

FGVAKVLDQL

³¹

GAKLVFTYRK

⁴¹

ERSRKELEKL

⁵¹

LEQLNQPEAH

⁶¹

LYQIDVQSDE

⁷¹

EVINGFEQIG

⁸¹

KDVGNIDGVY

⁹¹

HSIAFANMED

¹⁰¹

LRGRFSETSR

¹¹¹

EGFLLAQDIS

¹²¹

SYSLTIVAHE

¹³¹

AKKLMPEGGS

¹⁴¹

IVATTYLGGE

¹⁵¹

FAVQNYNVMG

¹⁶¹

VAKASLEANV

¹⁷¹

KYLALDLGPD

¹⁸¹

NIRVNAISAG

¹⁹¹

PIRTLSAKGV

²⁰¹

GGFNTILKEI

²¹¹

EERAPLKRNV

²²¹

DQVEVGKTAA

²³¹

YLLSDLSSGV

²⁴¹

TGENIHVDSG

²⁵¹

FHAIK

Residue

Distance (Å)

GLY13

2.816

ILE14

3.544

ALA15

3.470

ASN16

4.723

ARG18

4.727

SER19

2.208

ILE20

2.983

ALA21

4.671

TYR39

4.420

ARG40

2.901

LYS41

2.850

SER44

2.754

ILE65

3.347

ASP66

2.987

VAL67

3.169

GLN68

3.954

SER93

3.012

ILE94

3.377

Residue

Distance (Å)

ALA95

3.362

PHE96

4.070

ILE120

3.562

THR145

3.263

THR146

3.090

TYR147

3.450

TYR157

4.354

LYS164

2.655

ALA190

3.304

GLY191

3.561

PRO192

3.344

ILE193

2.965

THR195

2.703

LEU196

4.052

SER197

2.252

ALA198

4.647

PHE204

3.859

Ligand Name: 6-[4-(4-Hexyl-2-oxidanyl-phenoxy)phenoxy]pyridin-2-ol

Ligand Info

Structure Description

Crystal structure of S. aureus FabI inhibited by SKTS1

PDB:6YUR

Method

X-ray diffraction

Resolution

1.96 Å

Mutation

[7]

PDB Sequence

VNLENKTYVI

¹¹

MGIANKRSIA

²¹

FGVAKVLDQL

³¹

GAKLVFTYRK

⁴¹

ERSRKELEKL

⁵¹

LEQLNQPEAH

⁶¹

LYQIDVQSDE

⁷¹

EVINGFEQIG

⁸¹

KDVGNIDGVY

⁹¹

HSIAFANMED

¹⁰¹

LRGRFSETSR

¹¹¹

EGFLLAQDIS

¹²¹

SYSLTIVAHE

¹³¹

AKKLMPEGGS

¹⁴¹

IVATTYLGGE

¹⁵¹

FAVQNYNVMG

¹⁶¹

VAKASLEANV

¹⁷¹

KYLALDLGPD

¹⁸¹

NIRVNAISAG

¹⁹¹

PIRTLSAKGV

²⁰¹

GGFNTILKEI

²¹¹

EERAPLKRNV

²²¹

DQVEVGKTAA

²³¹

YLLSDLSSGV

²⁴¹

TGENIHVDSG

²⁵¹

FHAIK

Residue

Distance (Å)

ALA95

3.570

PHE96

3.508

ALA97

2.744

ASN98

4.517

MET99

3.648

LEU102

3.688

TYR147

3.681

VAL154

4.142

GLN155

3.163

ASN156

4.067

TYR157

2.484

MET160

3.792

Residue

Distance (Å)

LYS164

3.719

PRO192

4.123

THR195

4.667

LEU196

4.534

SER197

3.107

ALA198

3.859

GLY200

4.071

VAL201

3.686

GLY202

3.661

GLY203

4.693

PHE204

3.788

ILE207

3.878

Click to View More Binding Site Information of This Target with Different Ligands

Different Human System Profiles of Target	Top
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

Different Human System Profiles of Target

Top

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

There is no similarity protein (E value < 0.005) for this target

Drug Property Profile of Target

Top

(1) Molecular Weight (mw) based Drug Clustering

(2) Octanol/Water Partition Coefficient (xlogp) based Drug Clustering

(3) Hydrogen Bond Donor Count (hbonddonor) based Drug Clustering

(4) Hydrogen Bond Acceptor Count (hbondacc) based Drug Clustering

(5) Rotatable Bond Count (rotbonds) based Drug Clustering

(6) Topological Polar Surface Area (polararea) based Drug Clustering

"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 Profiles in Patients

Top

Drug Resistance
Mutation (DRM)

Drug Resistance Mutation Info

Target Affiliated Biological Pathways

Top

KEGG Pathway

[+] 4 KEGG Pathways

Fatty acid biosynthesis

Biotin metabolism

Metabolic pathways

Fatty acid metabolism

References

Top

REF 1

In vitro activities of CG400549, a novel FabI inhibitor, against recently isolated clinical staphylococcal strains in Korea. Antimicrob Agents Chemother. 2007 Jul;51(7):2591-3.

REF 2

Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)

REF 3

Activity of AFN-1252, a novel FabI inhibitor, against Staphylococcus aureus in an in vitro pharmacodynamic model simulating human pharmacokinetics. J Chemother. 2013 Feb;25(1):32-5.

REF 4

ClinicalTrials.gov (NCT01593761) Phase 2a Study of CG400549 for the Treatment of cABSSSI Caused by Methicillin-resistant Staphylococcus Aureus. U.S. National Institutes of Health.

REF 5

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800021501)

REF 6

The MUT056399 inhibitor of FabI is a new antistaphylococcal compound. Antimicrob Agents Chemother. 2011 Oct;55(10):4692-7.

REF 7

A Long Residence Time Enoyl-Reductase Inhibitor Explores an Extended Binding Region with Isoenzyme-Dependent Tautomer Adaptation and Differential Substrate-Binding Loop Closure. ACS Infect Dis. 2021 Apr 9;7(4):746-758.

If You Find Any Error in Data or Bug in Web Service, Please Kindly Report It to Dr. Zhou and Dr. Zhang.

Prof. Yuzong CHEN

Prof. Feng ZHU