a tool for identifying drug-targetable redox-active disulphides

Substance-P receptor

Intramolecular

Cysteine 105 and cysteine 180

Cysteine 322 and cysteine 323

Cysteine 306 and cysteine 307

Cysteine 255 and cysteine 260

Cysteine 255 and cysteine 1188

Cysteine 255 and cysteine 255

Cysteine 1004 and cysteine 255

A redox-regulated disulphide may form within Substance-P receptor between cysteines 105 and 180.

Details

Redox score ?

85

PDB code

Structure name

crystal structure of the neurokinin 1 receptor in complex with the small molecule antagonist netupitant

Structure deposition date

2018-09-11

Thiol separation (Å)

2

Half-sphere exposure sum ?

66

Minimum pK_a ?

nan

% buried

nan

Peptide accession

Residue number A

105

Residue number B

180

Peptide name

Substance-P receptor

Ligandability

Cysteine 105 of Substance-P receptor

Not ligandable in the dataset of Yang et al.

Not ligandable in the dataset of Yan et al.

Not ligandable in the dataset of Backus et al.

Not ligandable in the dataset of Vinogradova et al.

Not ligandable in the dataset of Cao et al.

Not ligandable in the dataset of Kuljanin et al.

Cysteine 180 of Substance-P receptor

Not ligandable in the dataset of Yang et al.

Not ligandable in the dataset of Yan et al.

Not ligandable in the dataset of Backus et al.

Not ligandable in the dataset of Vinogradova et al.

Not ligandable in the dataset of Cao et al.

Not ligandable in the dataset of Kuljanin et al.

A redox-regulated disulphide may form within Substance-P receptor between cysteines 322 and 323.

Details

Redox score ?

79

PDB code

Structure name

solution conformation of substance p in water complexed with nk1r

Structure deposition date

2009-12-31

Thiol separation (Å)

4

Half-sphere exposure sum ?

32

Minimum pK_a ?

8

% buried

0

Peptide accession

Residue number A

322

Residue number B

323

Peptide name

Substance-P receptor

Ligandability

Cysteine 322 of Substance-P receptor

Not ligandable in the dataset of Yang et al.

Not ligandable in the dataset of Yan et al.

Not ligandable in the dataset of Backus et al.

Not ligandable in the dataset of Vinogradova et al.

Not ligandable in the dataset of Cao et al.

Not ligandable in the dataset of Kuljanin et al.

Cysteine 323 of Substance-P receptor

Not ligandable in the dataset of Yang et al.

Not ligandable in the dataset of Yan et al.

Not ligandable in the dataset of Backus et al.

Not ligandable in the dataset of Vinogradova et al.

Not ligandable in the dataset of Cao et al.

Not ligandable in the dataset of Kuljanin et al.

A redox-regulated disulphide may form within Substance-P receptor between cysteines 306 and 307.

Details

Redox score ?

64

PDB code

Structure name

crystal structure of the human nk1 tachykinin receptor

Structure deposition date

2018-07-19

Thiol separation (Å)

6

Half-sphere exposure sum ?

46

Minimum pK_a ?

9

% buried

12

Peptide accession

Residue number A

306

Residue number B

307

Peptide name

Substance-P receptor

Ligandability

Cysteine 306 of Substance-P receptor

Not ligandable in the dataset of Yang et al.

Not ligandable in the dataset of Yan et al.

Not ligandable in the dataset of Backus et al.

Not ligandable in the dataset of Vinogradova et al.

Not ligandable in the dataset of Cao et al.

Not ligandable in the dataset of Kuljanin et al.

Cysteine 307 of Substance-P receptor

Not ligandable in the dataset of Yang et al.

Not ligandable in the dataset of Yan et al.

Not ligandable in the dataset of Backus et al.

Not ligandable in the dataset of Vinogradova et al.

Not ligandable in the dataset of Cao et al.

Not ligandable in the dataset of Kuljanin et al.

A redox-regulated disulphide may form within Substance-P receptor between cysteines 255 and 260. However, the redox score of this cysteine pair is lower than any known redox-active intermolecular disulphide. ?

Details

Redox score ?

39

PDB code

Structure name

human neurokinin 1 receptor (nk1r) substance p gs complex

Structure deposition date

2021-06-29

Thiol separation (Å)

10

Half-sphere exposure sum ?

49

Minimum pK_a ?

9

% buried

26

Peptide accession

Residue number A

255

Residue number B

260

Peptide name

Substance-P receptor

Ligandability

Cysteine 255 of Substance-P receptor

Not ligandable in the dataset of Yang et al.

Not ligandable in the dataset of Yan et al.

Not ligandable in the dataset of Backus et al.

Not ligandable in the dataset of Vinogradova et al.

Not ligandable in the dataset of Cao et al.

Not ligandable in the dataset of Kuljanin et al.

Cysteine 260 of Substance-P receptor

Not ligandable in the dataset of Yang et al.

Not ligandable in the dataset of Yan et al.

Not ligandable in the dataset of Backus et al.

Not ligandable in the dataset of Vinogradova et al.

Not ligandable in the dataset of Cao et al.

Not ligandable in the dataset of Kuljanin et al.

A redox-regulated disulphide may form within Substance-P receptor between cysteines 255 and 1188 (1133 and 1188 respectively in this structure).

Details

Redox score ?

nan

PDB code

Structure name

crystal structure of the human nk1 tachykinin receptor

Structure deposition date

2018-07-19

Thiol separation (Å)

10

Half-sphere exposure sum ?

76

Minimum pK_a ?

12

% buried

78

Peptide accession

Residue number A

255

Residue number B

1188

Peptide name

Substance-P receptor

Ligandability

Cysteine 255 of Substance-P receptor

Not ligandable in the dataset of Yang et al.

Not ligandable in the dataset of Yan et al.

Not ligandable in the dataset of Backus et al.

Not ligandable in the dataset of Vinogradova et al.

Not ligandable in the dataset of Cao et al.

Not ligandable in the dataset of Kuljanin et al.

Cysteine 1188 of Substance-P receptor

Not ligandable in the dataset of Yang et al.

Not ligandable in the dataset of Yan et al.

Not ligandable in the dataset of Backus et al.

Not ligandable in the dataset of Vinogradova et al.

Not ligandable in the dataset of Cao et al.

Not ligandable in the dataset of Kuljanin et al.

Cysteine 1188 in protein B could not be asigned to a Uniprot residue.

A redox-regulated disulphide may form within Substance-P receptor between cysteines 255 and 255 (1221 and 1350 respectively in this structure).

Details

Redox score ?

nan

PDB code

Structure name

crystal structure of the neurokinin 1 receptor in complex with the small molecule antagonist cp-99,994

Structure deposition date

2018-09-11

Thiol separation (Å)

5

Half-sphere exposure sum ?

68

Minimum pK_a ?

9

% buried

56

Peptide accession

Residue number A

255

Residue number B

255

Peptide name

Substance-P receptor

Ligandability

Cysteine 255 of Substance-P receptor

Not ligandable in the dataset of Yang et al.

Not ligandable in the dataset of Yan et al.

Not ligandable in the dataset of Backus et al.

Not ligandable in the dataset of Vinogradova et al.

Not ligandable in the dataset of Cao et al.

Not ligandable in the dataset of Kuljanin et al.

Cysteine 255 of Substance-P receptor

Not ligandable in the dataset of Yang et al.

Not ligandable in the dataset of Yan et al.

Not ligandable in the dataset of Backus et al.

Not ligandable in the dataset of Vinogradova et al.

Not ligandable in the dataset of Cao et al.

Not ligandable in the dataset of Kuljanin et al.

Uncertain whether structure cysteine 1221 has been assigned to correct residue.

A redox-regulated disulphide may form within Substance-P receptor between cysteines 1004 and 255 (1004 and 1133 respectively in this structure).

Details

Redox score ?

nan

PDB code

Structure name

crystal structure of the human nk1 tachykinin receptor

Structure deposition date

2018-07-19

Thiol separation (Å)

5

Half-sphere exposure sum ?

66

Minimum pK_a ?

10

% buried

50

Peptide accession

Residue number A

1004

Residue number B

255

Peptide name

Substance-P receptor

Ligandability

Cysteine 1004 of Substance-P receptor

Not ligandable in the dataset of Yang et al.

Not ligandable in the dataset of Yan et al.

Not ligandable in the dataset of Backus et al.

Not ligandable in the dataset of Vinogradova et al.

Not ligandable in the dataset of Cao et al.

Not ligandable in the dataset of Kuljanin et al.

Cysteine 255 of Substance-P receptor

Not ligandable in the dataset of Yang et al.

Not ligandable in the dataset of Yan et al.

Not ligandable in the dataset of Backus et al.

Not ligandable in the dataset of Vinogradova et al.

Not ligandable in the dataset of Cao et al.

Not ligandable in the dataset of Kuljanin et al.

Cysteine 1004 in protein A could not be asigned to a Uniprot residue.

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