a tool for identifying drug-targetable redox-active disulphides

Mucolipin-1

Intramolecular

Cysteine 253 and cysteine 284

Cysteine 166 and cysteine 192

Cysteine 429 and cysteine 430

Cysteine 430 and cysteine 431

Cysteine 309 and cysteine 316

Cysteine 429 and cysteine 431

Cysteine 440 and cysteine 463

A redox-regulated disulphide may form within Mucolipin-1 between cysteines 253 and 284.

Details

Redox score ?

86

PDB code

Structure name

i-ii linker of trpml1 channel at ph 7

Structure deposition date

2016-10-04

Thiol separation (Å)

2

Half-sphere exposure sum ?

46

Minimum pK_a ?

nan

% buried

nan

Peptide accession

Residue number A

253

Residue number B

284

Peptide name

Mucolipin-1

Ligandability

Cysteine 253 of Mucolipin-1

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 284 of Mucolipin-1

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 Mucolipin-1 between cysteines 166 and 192.

Details

Redox score ?

84

PDB code

Structure name

i-ii linker of trpml1 channel at ph 6

Structure deposition date

2016-10-04

Thiol separation (Å)

2

Half-sphere exposure sum ?

60

Minimum pK_a ?

nan

% buried

nan

Peptide accession

Residue number A

166

Residue number B

192

Peptide name

Mucolipin-1

Ligandability

Cysteine 166 of Mucolipin-1

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 192 of Mucolipin-1

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 Mucolipin-1 between cysteines 429 and 430. However, the redox score of this cysteine pair is lower than any known redox-active intermolecular disulphide. ?

Details

Redox score ?

60

PDB code

Structure name

cryo-em structure of mammalian endolysosomal trpml1 channel in nanodiscs in closed i conformation at 3

Structure deposition date

2017-08-07

Thiol separation (Å)

6

Half-sphere exposure sum ?

47

Minimum pK_a ?

9

% buried

26

Peptide accession

Residue number A

429

Residue number B

430

Peptide name

Mucolipin-1

Ligandability

Cysteine 429 of Mucolipin-1

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 430 of Mucolipin-1

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 Mucolipin-1 between cysteines 430 and 431. However, the redox score of this cysteine pair is lower than any known redox-active intermolecular disulphide. ?

Details

Redox score ?

55

PDB code

Structure name

human trpml1 channel structure in closed conformation

Structure deposition date

2017-07-21

Thiol separation (Å)

6

Half-sphere exposure sum ?

57

Minimum pK_a ?

10

% buried

43

Peptide accession

Residue number A

430

Residue number B

431

Peptide name

Mucolipin-1

Ligandability

Cysteine 430 of Mucolipin-1

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 431 of Mucolipin-1

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 Mucolipin-1 between cysteines 309 and 316. However, the redox score of this cysteine pair is lower than any known redox-active intermolecular disulphide. ?

Details

Redox score ?

42

PDB code

Structure name

cryo-em structure of mammalian endolysosomal trpml1 channel in nanodiscs in closed ii conformation at 3

Structure deposition date

2017-08-07

Thiol separation (Å)

9

Half-sphere exposure sum ?

66

Minimum pK_a ?

10

% buried

61

Peptide accession

Residue number A

309

Residue number B

316

Peptide name

Mucolipin-1

Ligandability

Cysteine 309 of Mucolipin-1

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 316 of Mucolipin-1

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 Mucolipin-1 between cysteines 429 and 431. However, the redox score of this cysteine pair is lower than any known redox-active intermolecular disulphide. ?

Details

Redox score ?

38

PDB code

Structure name

structure of human trpml1 with ml-si3

Structure deposition date

2021-04-12

Thiol separation (Å)

9

Half-sphere exposure sum ?

57

Minimum pK_a ?

11

% buried

73

Peptide accession

Residue number A

429

Residue number B

431

Peptide name

Mucolipin-1

Ligandability

Cysteine 429 of Mucolipin-1

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 431 of Mucolipin-1

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 Mucolipin-1 between cysteines 440 and 463. However, the redox score of this cysteine pair is lower than any known redox-active intermolecular disulphide. ?

Details

Redox score ?

32

PDB code

Structure name

cryo-em structure of human trpml1 with ml-sa1 and pi35p2

Structure deposition date

2018-07-27

Thiol separation (Å)

9

Half-sphere exposure sum ?

73

Minimum pK_a ?

12

% buried

94

Peptide accession

Residue number A

440

Residue number B

463

Peptide name

Mucolipin-1

Ligandability

Cysteine 440 of Mucolipin-1

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 463 of Mucolipin-1

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.

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