Target Information

Target General Information

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Target ID

T64410 (Former ID: TTDS00182)

Target Name

Bacterial DD-carboxypeptidase (Bact vanYB)

Synonyms

vanYB; DD-peptidase; DD-carboxypeptidase; D-alanyl-D-alanine carboxypeptidase-transpeptidase

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Gene Name

Bact vanYB

Target Type

Successful target

[1]

Disease

[+] 1 Target-related Diseases

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

Function

Vancomycin-inducible, penicillin-resistant, DD- carboxypeptidase that hydrolyzes depsipeptide- and D-alanyl-D- alanine-containing peptidoglycan precursors. Insensitive to beta- lactams.

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BioChemical Class

Peptidase

UniProt ID

VANY_ENTFA

EC Number

EC 3.4.16.4

Sequence

MEKSNYHSNVNHHKRHMKQSGEKRAFLWAFIISFTVCTLFLGWRLVSVLEATQLPPIPAT
HTGSGTGVAENPEENTLATAKEQGDEQEWSLILVNRQNPIPAQYDVELEQLSNGERIDIR
ISPYLQDLFDAARADGVYPIVASGYRTTEKQQEIMDEKVAEYKAKGYTSAQAKAEAETWV
AVPGTSEHQLGLAVDINADGIHSTGNEVYRWLDENSYRFGFIRRYPPDKTEITGVSNEPW
HYRYVGIEAATKIYHQGLCLEEYLNTEK

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3D Structure

Click to Show 3D Structure of This Target

PDB

Drugs and Modes of Action

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Approved Drug(s)

[+] 4 Approved Drugs

B-Lactams

Drug Info

Approved

Bacterial infection

[2]

Cefalotin

Drug Info

Approved

Bacterial infection

[3]

Cefotaxime

Drug Info

Approved

Bacterial infection

[4]

Cephalosporin

Drug Info

Approved

Bacterial infection

[5]

Clinical Trial Drug(s)

[+] 1 Clinical Trial Drugs

TD-1792

Drug Info

Phase 3

Skin infection

[6]

Mode of Action

[+] 2 Modes of Action

Inhibitor

[+] 14 Inhibitor drugs

B-Lactams

Drug Info

[2]

Cefalotin

Drug Info

[7]

Cefotaxime

Drug Info

[1], [7]

TD-1792

Drug Info

[9]

2-[(Dioxidophosphino)Oxy]Benzoate

Drug Info

[10]

3-boronobenzoic acid

Drug Info

[11]

5-boronothiophene-2-carboxylic acid

Drug Info

[11]

Benzo[c][1,2]oxaborol-1(3H)-ol

Drug Info

[11]

Cephalosporin C

Drug Info

[12]

D-Alanine

Drug Info

[10]

Formaldehyde

Drug Info

[10]

Glycyl-L-Alpha-Amino-Epsilon-Pimelyl-D-Alanine

Drug Info

[10]

NITROCEFIN

Drug Info

[13]

Phenyl Boronic acid

Drug Info

[11]

Binder

[+] 1 Binder drugs

Cephalosporin

Drug Info

[8]

Drug Binding Sites of Target

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Ligand Name: D-Alanine

Ligand Info

Structure Description

VanYB in complex with D-Alanine-D-Alanine

PDB:5ZHW

Method

X-ray diffraction

Resolution

2.18 Å

Mutation

[14]

PDB Sequence

EWSLILVNRQ

⁹⁷

NPIPAQYDVE

¹⁰⁷

LEQLSNGERI

¹¹⁷

DIRISPYLQD

¹²⁷

LFDAARADGV

¹³⁷

YPIVASGYRT

¹⁴⁷

TEKQQEIDEK

¹⁵⁸

VAEYKAKGYT

¹⁶⁸

SAQAKAEAET

¹⁷⁸

WVAVPGTSEH

¹⁸⁸

QLGLAVDINA

¹⁹⁸

DGIHSTGNEV

²⁰⁸

YRWLDENSYR

²¹⁸

FGFIRRYPPD

²²⁸

KTEITGVSNE

²³⁸

PWHYRYVGIE

²⁴⁸

AATKIYHQGL

²⁵⁸

CLEEYLNTEK

²⁶⁸

Residue

Distance (Å)

ARG146

3.494

GLN151

3.029

ILE154

3.943

TRP179

3.052

VAL180

3.751

ALA181

3.091

SER186

2.538

GLU187

3.868

Residue

Distance (Å)

HIS188

3.434

ASP195

3.141

TYR225

3.826

VAL235

4.114

GLU238

3.265

TRP240

3.575

HIS241

3.146

Click to View More Binding Site Information of This Target and Ligand Pair

Ligand Name: Selenomethionine

Ligand Info

Structure Description

VanYB in complex with D-Alanine-D-Alanine

PDB:5ZHW

Method

X-ray diffraction

Resolution

2.18 Å

Mutation

[14]

PDB Sequence

EWSLILVNRQ

⁹⁷

NPIPAQYDVE

¹⁰⁷

LEQLSNGERI

¹¹⁷

DIRISPYLQD

¹²⁷

LFDAARADGV

¹³⁷

YPIVASGYRT

¹⁴⁷

TEKQQEIDEK

¹⁵⁸

VAEYKAKGYT

¹⁶⁸

SAQAKAEAET

¹⁷⁸

WVAVPGTSEH

¹⁸⁸

QLGLAVDINA

¹⁹⁸

DGIHSTGNEV

²⁰⁸

YRWLDENSYR

²¹⁸

FGFIRRYPPD

²²⁸

KTEITGVSNE

²³⁸

PWHYRYVGIE

²⁴⁸

AATKIYHQGL

²⁵⁸

CLEEYLNTEK

²⁶⁸

Residue

Distance (Å)

LYS150

4.976

GLN151

2.930

GLN152

3.248

GLU153

3.190

ILE154

1.330

ASP156

1.333

GLU157

3.199

LYS158

3.168

Residue

Distance (Å)

VAL159

2.885

LYS173

4.514

ALA176

4.424

GLU177

4.086

VAL180

3.676

ALA181

4.212

VAL182

3.354

PRO183

3.803

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

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

Co-Targets

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Co-Targets

Co-Targets Info

Target-Related Models and Studies

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Target Validation

Target Validation Info

References

Top

REF 1

Extended-spectrum cephalosporinases: structure, detection and epidemiology. Future Microbiol. 2007 Jun;2:297-307.

REF 2

Has nature already identified all useful antibacterial targets Curr Opin Microbiol. 2008 Oct;11(5):387-92.

REF 3

Cefalotin - FDA approved drug information (drug label) from DailyMed.

REF 4

FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (ANDA) 064200.

REF 5

The Cephalosporin Antimicrobial Agents: A Comprehensive Review. J Vet Pharmacol Ther 11 (1):1-32. 1988.

REF 6

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

REF 7

Binding of cephalothin and cefotaxime to D-ala-D-ala-peptidase reveals a functional basis of a natural mutation in a low-affinity penicillin-binding protein and in extended-spectrum beta-lactamases. Biochemistry. 1995 Jul 25;34(29):9532-40.

REF 8

A 1.2-A snapshot of the final step of bacterial cell wall biosynthesis. Proc Natl Acad Sci U S A. 2001 Feb 13;98(4):1427-31.

REF 9

How many modes of action should an antibiotic have Curr Opin Pharmacol. 2008 Oct;8(5):564-73.

REF 10

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

REF 11

Synthesis and evaluation of 3-(dihydroxyboryl)benzoic acids as D,D-carboxypeptidase R39 inhibitors. J Med Chem. 2009 Oct 8;52(19):6097-106.

REF 12

DrugBank 3.0: a comprehensive resource for 'omics' research on drugs. Nucleic Acids Res. 2011 Jan;39(Database issue):D1035-41.

REF 13

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

REF 14

Structural basis for the substrate recognition of peptidoglycan pentapeptides by Enterococcus faecalis VanY(B). Int J Biol Macromol. 2018 Nov;119:335-344.

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