Target Information

Target General Information

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Target ID

T58093 (Former ID: TTDR00267)

Target Name

Staphylococcus Peptide deformylase (Stap-coc def)

Synonyms

def; Stap-coc Polypeptide deformylase

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Gene Name

Stap-coc def

Target Type

Clinical trial target

[1]

Disease

[+] 1 Target-related Diseases

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

Function

Removes the formyl group from the N-terminal Met of newly synthesized proteins. Requires at least a dipeptide for an efficient rate of reaction. N-terminal L-methionine is a prerequisite for activity but the enzyme has broad specificity at other positions.

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BioChemical Class

Carbon-nitrogen hydrolase

UniProt ID

DEF_STAAU

Sequence

MLTMKDIIRDGHPTLRQKAAELELPLTKEEKETLIAMREFLVNSQDEEIAKRYGLRSGVG
LAAPQINISKRMIAVLIPDDGSGKSYDYMLVNPKIVSHSVQEAYLPTGEGCLSVDDNVAG
LVHRHNRITIKAKDIEGNDIQLRLKGYPAIVFQHEIDHLNGVMFYDHIDKNHPLQPHTDA
VEV

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3D Structure

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PDB

Drugs and Modes of Action

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Clinical Trial Drug(s)

[+] 1 Clinical Trial Drugs

GSK1322322

Drug Info

Phase 2

Bacterial infection

[1]

Mode of Action

[+] 2 Modes of Action

Modulator

[+] 1 Modulator drugs

GSK1322322

Drug Info

[1], [2]

Inhibitor

[+] 13 Inhibitor drugs

Actinonin

Drug Info

[3]

2-(3-BENZOYLPHENOXY)ETHYL(HYDROXY)FORMAMIDE

Drug Info

[4]

3-Sulfinoalanine

Drug Info

[5]

Bb-3497

Drug Info

[5]

Cysteinesulfonic Acid

Drug Info

[5]

Double Oxidized Cysteine

Drug Info

[5]

Formic Acid

Drug Info

[5]

HYDROXY[3-(6-METHYLPYRIDIN-2-YL)PROPYL]FORMAMIDE

Drug Info

[4]

N-(2-Acetamido)Iminodiacetic Acid

Drug Info

[5]

N-alkyl urea hydroxamic acids

Drug Info

[6]

NVP-PDF386

Drug Info

[7]

VRC3375

Drug Info

[8]

[HYDROXY(3-PHENYLPROPYL)AMINO]METHANOL

Drug Info

[4]

Drug Binding Sites of Target

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Ligand Name: 3-Sulfinoalanine

Ligand Info

Structure Description

Crystal Structures of Peptide Deformylase from Staphylococcus aureus Complexed with Actinonin

PDB:1Q1Y

Method

X-ray diffraction

Resolution

1.90 Å

Mutation

Yes

[9]

PDB Sequence

MLTMKDIIRD

¹⁰

GHPTLRQKAA

²⁰

ELELPLTKEE

³⁰

KETLIAMREF

⁴⁰

LVNSQDEEIA

⁵⁰

KRYGLRSGVG

⁶⁰

LAAPQINISK

⁷⁰

RMIAVLIPDD

⁸⁰

GSGKSYDYML

⁹⁰

VNPKIVSHSV

¹⁰⁰

QEAYLPTGEG

¹¹⁰

LSVDDNVAGL

¹²¹

VHRHNRITIK

¹³¹

AKDIEGNDIQ

¹⁴¹

LRLKGYPAIV

¹⁵¹

FQHEIDHLNG

¹⁶¹

VMFYDHIDKD

¹⁷¹

HPLQPHTDAV

¹⁸¹

EVLEH

Residue

Distance (Å)

ARG56

2.804

GLN65

2.924

GLU109

4.510

GLY110

1.328

LEU112

1.330

SER113

2.667

Residue

Distance (Å)

VAL114

2.918

ASP115

4.803

HIS154

3.754

HIS158

3.223

MET163

3.038

PHE164

3.545

Ligand Name: Actinonin

Ligand Info

Structure Description

Crystal Structures of Peptide Deformylase from Staphylococcus aureus Complexed with Actinonin

PDB:1Q1Y

Method

X-ray diffraction

Resolution

1.90 Å

Mutation

Yes

[9]

PDB Sequence

MLTMKDIIRD

¹⁰

GHPTLRQKAA

²⁰

ELELPLTKEE

³⁰

KETLIAMREF

⁴⁰

LVNSQDEEIA

⁵⁰

KRYGLRSGVG

⁶⁰

LAAPQINISK

⁷⁰

RMIAVLIPDD

⁸⁰

GSGKSYDYML

⁹⁰

VNPKIVSHSV

¹⁰⁰

QEAYLPTGEG

¹¹⁰

LSVDDNVAGL

¹²¹

VHRHNRITIK

¹³¹

AKDIEGNDIQ

¹⁴¹

LRLKGYPAIV

¹⁵¹

FQHEIDHLNG

¹⁶¹

VMFYDHIDKD

¹⁷¹

HPLQPHTDAV

¹⁸¹

EVLEH

Residue

Distance (Å)

ARG56

3.404

SER57

3.323

GLY58

3.223

VAL59

2.797

GLY60

3.131

LEU61

4.368

ALA62

4.655

GLN65

2.725

LEU105

3.517

GLU109

3.411

Residue

Distance (Å)

GLY110

3.590

LEU112

2.702

SER113

4.559

TYR147

4.425

ILE150

3.665

VAL151

3.663

HIS154

3.363

GLU155

2.688

HIS158

2.924

GLU185

3.691

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

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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

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

Chemical Structure based Activity Landscape of Target

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Drug Property Profile of Target

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(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 Poor or Non Binders

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Target Poor or Non Binders

Target Poor or Non Binders Info

Target-Related Models and Studies

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Target QSAR Model

References

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REF 1

Peptide deformylase: a new target in antibacterial, antimalarial and anticancer drug discovery. Curr Med Chem. 2015;22(2):214-36.

REF 2

Comparative analysis of the antibacterial activity of a novel peptide deformylase inhibitor, GSK1322322. Antimicrob Agents Chemother. 2013 May;57(5):2333-42.

REF 3

Actinonin, a naturally occurring antibacterial agent, is a potent deformylase inhibitor. Biochemistry. 2000 Feb 15;39(6):1256-62.

REF 4

The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42.

REF 5

How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.

REF 6

N-alkyl urea hydroxamic acids as a new class of peptide deformylase inhibitors with antibacterial activity. Antimicrob Agents Chemother. 2002 Sep;46(9):2752-64.

REF 7

Comparative spectrum and activity of NVP-PDF386 (VRC4887), a new peptide deformylase inhibitor. J Antimicrob Chemother. 2003 Jan;51(1):157-61.

REF 8

Peptide deformylase inhibitors as antibacterial agents: identification of VRC3375, a proline-3-alkylsuccinyl hydroxamate derivative, by using an integrated combinatorial and medicinal chemistry approach. Antimicrob Agents Chemother. 2004 Jan;48(1):250-61.

REF 9

Crystal structure of peptide deformylase from Staphylococcus aureus in complex with actinonin, a naturally occurring antibacterial agent. Proteins. 2004 Nov 15;57(3):639-42.

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