Target Information

Target General Information

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Target ID

T59445 (Former ID: TTDR00879)

Target Name

Sorbitoldehydrogenase (SORD)

Synonyms

SORD; SDH; L-iditol2-dehydrogenase

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Gene Name

SORD

Target Type

Literature-reported target

[1]

Function

Convertssorbitol to fructose. Part of the polyol pathway that plays an important role in sperm physiology. May play a role in the sperm motility by providing an energetic source for sperm.

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BioChemical Class

Short-chain dehydrogenases reductase

UniProt ID

DHSO_HUMAN

EC Number

EC 1.1.1.-

Sequence

MAAAAKPNNLSLVVHGPGDLRLENYPIPEPGPNEVLLRMHSVGICGSDVHYWEYGRIGNF
IVKKPMVLGHEASGTVEKVGSSVKHLKPGDRVAIEPGAPRENDEFCKMGRYNLSPSIFFC
ATPPDDGNLCRFYKHNAAFCYKLPDNVTFEEGALIEPLSVGIHACRRGGVTLGHKVLVCG
AGPIGMVTLLVAKAMGAAQVVVTDLSATRLSKAKEIGADLVLQISKESPQEIARKVEGQL
GCKPEVTIECTGAEASIQAGIYATRSGGNLVLVGLGSEMTTVPLLHAAIREVDIKGVFRY
CNTWPVAISMLASKSVNVKPLVTHRFPLEKALEAFETFKKGLGLKIMLKCDPSDQNP

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3D Structure

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PDB

ADReCS ID

BADD_A02053

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: Nicotinamide-Adenine-Dinucleotide

Ligand Info

Structure Description

human SDH/NAD+ complex

PDB:1PL8

Method

X-ray diffraction

Resolution

1.90 Å

Mutation

[3]

PDB Sequence

AAAAKPNNLS

¹⁰

LVVHGPGDLR

²⁰

LENYPIPEPG

³⁰

PNEVLLRMHS

⁴⁰

VGICGSDVHY

⁵⁰

WEYGRIGNFI

⁶⁰

VKKPMVLGHE

⁷⁰

ASGTVEKVGS

⁸⁰

SVKHLKPGDR

⁹⁰

VAIEPGAPRE

¹⁰⁰

NDEFCKMGRY

¹¹⁰

NLSPSIFFCA

¹²⁰

TPPDDGNLCR

¹³⁰

FYKHNAAFCY

¹⁴⁰

KLPDNVTFEE

¹⁵⁰

GALIEPLSVG

¹⁶⁰

IHACRRGGVT

¹⁷⁰

LGHKVLVCGA

¹⁸⁰

GPIGMVTLLV

¹⁹⁰

AKAMGAAQVV

²⁰⁰

VTDLSATRLS

²¹⁰

KAKEIGADLV

²²⁰

LQISKESPQE

²³⁰

IARKVEGQLG

²⁴⁰

CKPEVTIECT

²⁵⁰

GAEASIQAGI

²⁶⁰

YATRSGGTLV

²⁷⁰

LVGLGSEMTT

²⁸⁰

VPLLHAAIRE

²⁹⁰

VDIKGVFRYC

³⁰⁰

NTWPVAISML

³¹⁰

ASKSVNVKPL

³²⁰

VTHRFPLEKA

³³⁰

LEAFETFKKG

³⁴⁰

LGLKIMLKCD

³⁵⁰

PSDQNP

Residue

Distance (Å)

VAL159

4.070

CYS178

4.961

GLY179

3.907

ALA180

4.066

GLY181

3.274

PRO182

3.283

ILE183

3.018

GLY184

4.174

THR202

3.842

ASP203

2.505

LEU204

3.676

SER205

4.419

ARG208

2.805

Residue

Distance (Å)

ILE223

3.841

CYS249

3.124

THR250

3.361

GLY251

4.697

ALA252

3.809

ALA254

4.759

SER255

4.107

VAL272

3.077

GLY273

3.456

LEU274

2.935

VAL296

2.828

PHE297

3.609

ARG298

2.565

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

Ligand Name: 4-[2-(Hydroxymethyl)pyrimidin-4-YL]-N,N-dimethylpiperazine-1-sulfonamide

Ligand Info

Structure Description

Human SDH/NADH/inhibitor complex

PDB:1PL6

Method

X-ray diffraction

Resolution

2.00 Å

Mutation

Yes

[3]

PDB Sequence

AAAAKPNNLS

¹⁰

LVVHGPGDLR

²⁰

LENYPIPEPG

³⁰

PNEVLLRHSV

⁴¹

GICGSDVHYW

⁵¹

EYGRIGNFIV

⁶¹

KKPVLGHEAS

⁷²

GTVEKVGSSV

⁸²

KHLKPGDRVA

⁹²

IEPGAPREND

¹⁰²

EFCKGRYNLS

¹¹³

PSIFFCATPP

¹²³

DDGNLCRFYK

¹³³

HNAAFCYKLP

¹⁴³

DNVTFEEGAL

¹⁵³

IEPLSVGIHA

¹⁶³

CRRGGVTLGH

¹⁷³

KVLVCGAGPI

¹⁸³

GVTLLVAKAG

¹⁹⁵

AAQVVVTDLS

²⁰⁵

ATRLSKAKEI

²¹⁵

GADLVLQISK

²²⁵

ESPQEIARKV

²³⁵

EGQLGCKPEV

²⁴⁵

TIECTGAEAS

²⁵⁵

IQAGIYATRS

²⁶⁵

GGTLVLVGLG

²⁷⁵

SETTVPLLHA

²⁸⁶

AIREVDIKGV

²⁹⁶

FRYCNTWPVA

³⁰⁶

ISLASKSVNV

³¹⁷

KPLVTHRFPL

³²⁷

EKALEAFETF

³³⁷

KKGLGLKILK

³⁴⁸

CDPSDQNP

Residue

Distance (Å)

CYS44

3.373

SER46

3.337

TYR50

3.516

ILE56

3.535

PHE59

3.396

HIS69

3.009

PHE118

3.951

Residue

Distance (Å)

THR121

3.600

GLU155

2.389

VAL159

4.920

LEU274

3.506

PHE297

3.394

ARG298

3.917

TYR299

4.360

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 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

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


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
Pentose and glucuronate interconversions	hsa00040	Affiliated Target
Class: Metabolism => Carbohydrate metabolism	Pathway Hierarchy
Fructose and mannose metabolism	hsa00051	Affiliated Target
Class: Metabolism => Carbohydrate metabolism	Pathway Hierarchy

Degree	3	Degree centrality	3.22E-04	Betweenness centrality	2.13E-04
Closeness centrality	1.54E-01	Radiality	1.21E+01	Clustering coefficient	0.00E+00
Neighborhood connectivity	2.67E+00	Topological coefficient	3.33E-01	Eccentricity	12
Download	Click to Download the Full PPI Network of This Target

Chemical Structure based Activity Landscape of Target

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Target Poor or Non Binders

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Target Poor or Non Binders

Target Poor or Non Binders Info

Target Affiliated Biological Pathways

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BioCyc

[+] 1 BioCyc Pathways

Sorbitol degradation I

KEGG Pathway

[+] 3 KEGG Pathways

Pentose and glucuronate interconversions

Fructose and mannose metabolism

Metabolic pathways

NetPath Pathway

[+] 1 NetPath Pathways

TSH Signaling Pathway

Pathwhiz Pathway

[+] 1 Pathwhiz Pathways

Fructose and Mannose Degradation

WikiPathways

[+] 1 WikiPathways

Polyol Pathway

References

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REF 1

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

REF 2

Sorbitol dehydrogenase: a novel target for adjunctive protection of ischemic myocardium. FASEB J. 2003 Dec;17(15):2331-3.

REF 3

X-ray crystallographic and kinetic studies of human sorbitol dehydrogenase. Structure. 2003 Sep;11(9):1071-85.

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