Target Information

Target General Information

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Target ID

T67942 (Former ID: TTDR00871)

Target Name

Bacterial Cystathionine gamma-synthase (Bact metB)

Synonyms

metB; O-succinylhomoserine (Thiol)-lyase; CGS

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Gene Name

Bact metB

Target Type

Literature-reported target

[1]

Disease

[+] 1 Target-related Diseases

Chronic obstructive pulmonary disease [ICD-11: CA22]

Function

Catalyzes the formation of L-cystathionine from O- succinyl-L-homoserine (OSHS) and L-cysteine, via a gamma- replacement reaction. In the absence of thiol, catalyzes gamma- elimination to form 2-oxobutanoate, succinate and ammonia.

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BioChemical Class

Alkyl aryl transferase

UniProt ID

METB_ECOLI

EC Number

EC 2.5.1.48

Sequence

MTRKQATIAVRSGLNDDEQYGCVVPPIHLSSTYNFTGFNEPRAHDYSRRGNPTRDVVQRA
LAELEGGAGAVLTNTGMSAIHLVTTVFLKPGDLLVAPHDCYGGSYRLFDSLAKRGCYRVL
FVDQGDEQALRAALAEKPKLVLVESPSNPLLRVVDIAKICHLAREVGAVSVVDNTFLSPA
LQNPLALGADLVLHSCTKYLNGHSDVVAGVVIAKDPDVVTELAWWANNIGVTGGAFDSYL
LLRGLRTLVPRMELAQRNAQAIVKYLQTQPLVKKLYHPSLPENQGHEIAARQQKGFGAML
SFELDGDEQTLRRFLGGLSLFTLAESLGGVESLISHAATMTHAGMAPEARAAAGISETLL
RISTGIEDGEDLIADLENGFRAANKG

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3D Structure

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PDB

Drugs and Modes of Action

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Preclinical Drug(s)

[+] 1 Preclinical Drugs

GW-3333

Drug Info

Preclinical

Chronic obstructive pulmonary disease

[2]

Mode of Action

[+] 1 Modes of Action

Inhibitor

[+] 2 Inhibitor drugs

GW-3333

Drug Info

[1]

N'-Pyridoxyl-Lysine-5'-Monophosphate

Drug Info

[3]

Drug Binding Sites of Target

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Ligand Name: N6-((3-Hydroxy-2-methyl-5-((phosphonooxy)methyl)-4-pyridinyl)methylene)-L-lysine

Ligand Info

Structure Description

CYSTATHIONINE GAMMA-SYNTHASE (CGS) FROM ESCHERICHIA COLI

PDB:1CS1

Method

X-ray diffraction

Resolution

1.50 Å

Mutation

Yes

[4]

PDB Sequence

RKQATIAVRS

¹²

GLNDDEQYGC

²²

VVPPIHLSST

³²

YNFTGFNEPR

⁴²

AHDYSRRGNP

⁵²

TRDVVQRALA

⁶²

ELEGGAGAVL

⁷²

TNTGMSAIHL

⁸²

VTTVFLKPGD

⁹²

LLVAPHDCYG

¹⁰²

GSYRLFDSLA

¹¹²

KRGCYRVLFV

¹²²

DQGDEQALRA

¹³²

ALAEKPKLVL

¹⁴²

VESPSNPLLR

¹⁵²

VVDIAKICHL

¹⁶²

AREVGAVSVV

¹⁷²

DNTFLSPALQ

¹⁸²

NPLALGADLV

¹⁹²

LHSCTYLNGH

²⁰³

SDVVAGVVIA

²¹³

KDPDVVTELA

²²³

WWANNIGVTG

²³³

GAFDSYLLLR

²⁴³

GLRTLVPRME

²⁵³

LAQRNAQAIV

²⁶³

KYLQTQPLVK

²⁷³

KLYHPSLPEN

²⁸³

QGHEIAARQQ

²⁹³

KGFGAMLSFE

³⁰³

LDGDEQTLRR

³¹³

FLGGLSLFTL

³²³

AESLGGVESL

³³³

ISHAATMTHA

³⁴³

GMAPEARAAA

³⁵³

GISETLLRIS

³⁶³

TGIEDGEDLI

³⁷³

ADLENGFRAA

³⁸³

NKG

Residue

Distance (Å)

THR75

3.481

GLY76

2.854

MET77

2.794

ILE80

3.844

TYR101

3.450

SER104

4.823

GLU144

3.587

ASP173

2.699

THR175

3.572

PHE176

4.121

SER195

2.847

CYS196

2.986

Residue

Distance (Å)

THR197

1.325

TYR199

1.327

LEU200

3.429

ASN201

3.655

GLY202

2.878

HIS203

4.765

VAL207

4.402

ALA208

3.940

SER326

3.355

LEU327

3.407

GLY328

3.725

GLY329

4.587

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

References

Top

REF 1

Crystal structures of cystathionine gamma-synthase inhibitor complexes rationalize the increased affinity of a novel inhibitor. J Mol Biol. 2001 Aug 24;311(4):789-801.

REF 2

Emerging drugs for the treatment of chronic obstructive pulmonary disease. Expert Opin Emerg Drugs. 2006 May;11(2):275-91.

REF 3

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

REF 4

Crystal structure of Escherichia coli cystathionine gamma-synthase at 1.5 A resolution. EMBO J. 1998 Dec 1;17(23):6827-38.

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