About
Redox-active disulphides have emerged as key regulators of protein function, making them important both physiologically and in disease. Involved cysteines can be targeted as nucleophiles by covalent drugs, which can mediate potent biological effects.
ReDisulphID
(Redox Disulphide IDentifier)
is a bioinformatic tool that uses available structural data to predict the presence of novel redox-active disulphide bonds in mammalian proteins.
This has been achieved by searching all mammalian protein structures for cysteine pairs with thiols within 10 Å of each other in the RCSB protein databank. Finally, known redox-active disulphides were used to determine parameters to give a rating to potential novel redox-regulated disulphides, this rating is in the form of a % redox score.
HSE - Half sphere exposure
HSE is a measure of the accessibility of an amino acid side-chain. Cα atoms are counted in a 12 Å radius around the Cα of each cysteine in the potential redox-active disulphide bond. A lower HSE means an amino acid has fewer proximal amino acids, so is more accessible.
Minimum pKa
The lowest pKa from each thiol in the cystiene pair. A lower minimum pKa means a cysteine pair is more likely to form a redox-regulated disulphide bond. The pKa of the cysteine thiols in the potential redox-active disulphide bond are calculated using the PROPKA algorithm.
Redox Score
The redox score is related to how likely a cysteine pair is to form a redox active disulphide. It is calculated from solvent accessibility, pKa, and distance between each thiol in the cysteine pair. The highest redox score is 100.0, and the lowest redox score of a known redox-active intermolecular disulphide is 60, while the lowest score overall is 0.
Ligandability
Some cysteine pairs are known to be ligandable, meaning they can be targeted by covalent drugs. If a protein contains a disulphide with a ligandable cysteine, this is indicated by a tick in the ligandability column.
Duplicates
A particular cysteine pair often features in multiple structures, which would lead to duplicates. To remove duplicates, cysteines were assigned to a residue number in their UniProt sequence, then the structure where the cysteine thiols are closest to each other is chosen for that potential redox-active disulphide.
The most recent structure in this database is from 2023-01-11.