Target Information

Target General Information

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Target ID

T02587 (Former ID: TTDR01249)

Target Name

Pyridoxal phosphate phosphatase (PDXP)

Synonyms

PLPP; PLP phosphatase; PDXP

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Gene Name

PDXP

Target Type

Literature-reported target

[1]

Function

Protein serine phosphatase that dephosphorylates 'Ser-3' in cofilin and probably also dephosphorylates phospho-serine residues in DSTN. Regulates cofilin-dependent actin cytoskeleton reorganization. Required for normal progress through mitosis and normal cytokinesis. Does not dephosphorylate phospho-threonines in LIMK1. Does not dephosphorylate peptides containing phospho- tyrosine. Pyridoxal phosphate phosphatase. Has some activity towards pyridoxal 5'-phosphate (PLP), pyridoxine 5'-phosphate (PMP) and pyridoxine 5'-phosphate (PNP), with a highest activity with PLP followed by PNP.

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BioChemical Class

Phosphoric monoester hydrolase

UniProt ID

PLPP_HUMAN

EC Number

EC 3.1.3.3

Sequence

MARCERLRGAALRDVLGRAQGVLFDCDGVLWNGERAVPGAPELLERLARAGKAALFVSNN
SRRARPELALRFARLGFGGLRAEQLFSSALCAARLLRQRLPGPPDAPGAVFVLGGEGLRA
ELRAAGLRLAGDPSAGDGAAPRVRAVLVGYDEHFSFAKLREACAHLRDPECLLVATDRDP
WHPLSDGSRTPGTGSLAAAVETASGRQALVVGKPSPYMFECITENFSIDPARTLMVGDRL
ETDILFGHRCGMTTVLTLTGVSRLEEAQAYLAAGQHDLVPHYYVESIADLTEGLED

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3D Structure

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PDB

Cell-based Target Expression Variations

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Cell-based Target Expression Variations

Cell-based Target Expression Variations Info

Drug Binding Sites of Target

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Ligand Name: Pyridoxal phosphate

Ligand Info

Structure Description

Crystal structure of human pyridoxal 5'-phosphate phosphatase with its substrate

PDB:2CFT

Method

X-ray diffraction

Resolution

1.80 Å

Mutation

[2]

PDB Sequence

MARCERLRGA

¹⁰

ALRDVLGRAQ

²⁰

GVLFDCDGVL

³⁰

WNGERAVPGA

⁴⁰

PELLERLARA

⁵⁰

GKAALFVSNN

⁶⁰

SRRARPELAL

⁷⁰

RFARLGFGGL

⁸⁰

RAEQLFSSAL

⁹⁰

CAARLLRQRL

¹⁰⁰

PGPPDGAVFV

¹¹²

LGGEGLRAEL

¹²²

RAAGLRLAGD

¹³²

PSAGDGAAPR

¹⁴²

VRAVLVGYDE

¹⁵²

HFSFAKLREA

¹⁶²

CAHLRDPECL

¹⁷²

LVATDRDPWH

¹⁸²

PLSDGSRTPG

¹⁹²

TGSLAAAVET

²⁰²

ASGRQALVVG

²¹²

KPSPYMFECI

²²²

TENFSIDPAR

²³²

TLMVGDRLET

²⁴²

DILFGHRCGM

²⁵²

TTVLTLTGVS

²⁶²

RLEEAQAYLA

²⁷²

AGQHDLVPHY

²⁸²

YVESIADLTE

²⁹²

GLE

Residue

Distance (Å)

ASP25

3.103

CYS26

3.429

ASP27

2.985

VAL57

4.409

SER58

2.632

ASN59

2.843

ASN60

3.321

SER61

4.302

Residue

Distance (Å)

ARG62

4.541

TYR150

3.265

ASP179

4.095

HIS182

3.310

THR190

4.988

LYS213

2.899

ASP238

4.538

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Ligand Name: Selenomethionine

Ligand Info

Structure Description

Crystal structure of human pyridoxal phosphate phosphatase

PDB:2OYC

Method

X-ray diffraction

Resolution

1.72 Å

Mutation

[3]

PDB Sequence

SLARCERLRG

⁹

AALRDVLGRA

¹⁹

QGVLFDCDGV

²⁹

LWNGERAVPG

³⁹

APELLERLAR

⁴⁹

AGKAALFVSN

⁵⁹

NSRRARPELA

⁶⁹

LRFARLGFGG

⁷⁹

LRAEQLFSSA

⁸⁹

LCAARLLRQR

⁹⁹

LPGPPDAPGA

¹⁰⁹

VFVLGGEGLR

¹¹⁹

AELRAAGLRL

¹²⁹

AGDPSAGAPR

¹⁴²

VRAVLVGYDE

¹⁵²

HFSFAKLREA

¹⁶²

CAHLRDPECL

¹⁷²

LVATDRDPWH

¹⁸²

PLSDGSRTPG

¹⁹²

TGSLAAAVET

²⁰²

ASGRQALVVG

²¹²

KPSPYFECIT

²²³

ENFSIDPART

²³³

LVGDRLETDI

²⁴⁴

LFGHRCGTTV

²⁵⁵

LTLTGVSRLE

²⁶⁵

EAQAYLAAGQ

²⁷⁵

HDLVPHYYVE

²⁸⁵

SIADLTEGL

Residue

Distance (Å)

LEU23

3.610

PHE24

4.446

ASP25

3.989

VAL57

3.073

SER58

4.040

ASN59

3.584

SER87

4.151

SER88

4.038

CYS91

3.558

VAL211

3.877

GLY212

3.880

LYS213

2.853

SER215

4.224

PRO216

3.143

TYR217

1.335

PHE219

1.326

GLU220

3.282

CYS221

3.215

Residue

Distance (Å)

ILE222

2.957

PRO230

3.468

THR233

3.468

LEU234

1.333

VAL236

1.335

GLY237

4.142

ASP243

3.661

ILE244

4.892

PHE246

3.773

GLY247

2.909

HIS248

4.651

CYS250

3.422

GLY251

1.333

THR253

1.326

THR254

3.458

VAL255

2.781

HIS281

3.581

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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 Tissue Distribution of target is determined from a proteomics study that quantified more than 12,000 genes across 32 normal human tissues. Tissue Specificity (TS) score was used to define the enrichment of target across tissues. The distribution of targets among different tissues or organs need to be taken into consideration when assessing the target druggability, as it is generally accepted that the wider the target distribution, the greater the concern over potential adverse effects (Nat Rev Drug Discov, 20: 64-81, 2021). Human Pathway Affiliation of target is determined by the life-essential pathways provided on KEGG database. The target-affiliated pathways were defined based on the following two criteria (a) the pathways of the studied target should be life-essential for both healthy individuals and patients, and (b) the studied target should occupy an upstream position in the pathways and therefore had the ability to regulate biological function. Targets involved in a fewer pathways have greater likelihood to be successfully developed, while those associated with more human pathways increase the chance of undesirable interferences with other human processes (Pharmacol Rev, 58: 259-279, 2006). Biological Network Descriptors of target is determined based on a human protein-protein interactions (PPI) network consisting of 9,309 proteins and 52,713 PPIs, which were with a high confidence score of ≥ 0.95 collected from STRING database. The network properties of targets based on protein-protein interactions (PPIs) have been widely adopted for the assessment of target’s druggability. Proteins with high node degree tend to have a high impact on network function through multiple interactions, while proteins with high betweenness centrality are regarded to be central for communication in interaction networks and regulate the flow of signaling information (Front Pharmacol, 9, 1245, 2018; Curr Opin Struct Biol. 44:134-142, 2017). Human Similarity Proteins Human Tissue Distribution Human Pathway Affiliation Biological Network Descriptors

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 Tissue Distribution of target is determined from a proteomics study that quantified more than 12,000 genes across 32 normal human tissues. Tissue Specificity (TS) score was used to define the enrichment of target across tissues.

The distribution of targets among different tissues or organs need to be taken into consideration when assessing the target druggability, as it is generally accepted that the wider the target distribution, the greater the concern over potential adverse effects (Nat Rev Drug Discov, 20: 64-81, 2021).

Human Pathway Affiliation of target is determined by the life-essential pathways provided on KEGG database. The target-affiliated pathways were defined based on the following two criteria (a) the pathways of the studied target should be life-essential for both healthy individuals and patients, and (b) the studied target should occupy an upstream position in the pathways and therefore had the ability to regulate biological function.

Targets involved in a fewer pathways have greater likelihood to be successfully developed, while those associated with more human pathways increase the chance of undesirable interferences with other human processes (Pharmacol Rev, 58: 259-279, 2006).

Biological Network Descriptors of target is determined based on a human protein-protein interactions (PPI) network consisting of 9,309 proteins and 52,713 PPIs, which were with a high confidence score of ≥ 0.95 collected from STRING database.

The network properties of targets based on protein-protein interactions (PPIs) have been widely adopted for the assessment of target’s druggability. Proteins with high node degree tend to have a high impact on network function through multiple interactions, while proteins with high betweenness centrality are regarded to be central for communication in interaction networks and regulate the flow of signaling information (Front Pharmacol, 9, 1245, 2018; Curr Opin Struct Biol. 44:134-142, 2017).

Human Similarity Proteins

Human Tissue Distribution

Human Pathway Affiliation

Biological Network Descriptors

Protein Name	Pfam ID	Percentage of Identity (%)	E value
N-acylneuraminate-9-phosphatase (NANP)	PF13419	30.435 (35/115)	2.38E-04


Note: If a protein has TS (tissue specficity) scores at least in one tissue >= 2.5, this protein is called tissue-enriched (including tissue-enriched-but-not-specific and tissue-specific). In the plots, the vertical lines are at thresholds 2.5 and 4.

KEGG Pathway	Pathway ID	Affiliated Target	Pathway Map
Vitamin B6 metabolism	hsa00750	Affiliated Target
Class: Metabolism => Metabolism of cofactors and vitamins	Pathway Hierarchy

Degree	2	Degree centrality	2.15E-04	Betweenness centrality	6.07E-04
Closeness centrality	2.24E-01	Radiality	1.39E+01	Clustering coefficient	0.00E+00
Neighborhood connectivity	6.85E+01	Topological coefficient	5.00E-01	Eccentricity	11
Download	Click to Download the Full PPI Network of This Target

References

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REF 1

Thiamine status in liver and brain of rats genetically selected for different sensitivity to hypnotic effect of alcohol. Alcohol Clin Exp Res. 2000 Nov;24(11):1620-4.

REF 2

Crystal Structure of Human Pyridoxal 5-Phosphate Phosphatase

REF 3

Structural genomics of protein phosphatases. J Struct Funct Genomics. 2007 Sep;8(2-3):121-40.

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