Protein damage susceptibility

Protein damage (partly followed by protein aggregation) plays a significant role in ageing, cancer and in neurodegenerative and other diseases. It is known that the proteinogenic amino acids differ in their susceptibility to non-enzymatic modification, such as hydroxylation, peroxidation, chlorination etc. (Fichtner et al., 2020)


More graphics: damage.stark-jena.de


Amino acid Modification Höhn et al. 2013 Davies
2004
Stadtman and Levine 2003 Berlett and Stadtman 1997 Key amino acids Key Modification
G (Glycine) Aminomalonic acid
X

aliphatic Carbonylation
I (Isoleucine) Carbonyls
X

sulfuric Peroxidation

Hydroperoxides (unstable)
X

alkalic Hydroxylation

Alcohols
X

acidic Sulfur oxidation
L (Leucine) A-ketoisocaproic acid
X

aromatic Nitration

Carbonyls
X

polar Chlorination

Hydroperoxides (unstable)
X


Bromination

Alcohols
X


Dimerization

3-Hydroxyleucine X
X

Other

4-Hydroxyleucine X
X



5-Hydroxyleucine X
X



Isovaleric acid
X




Isovaleraldehyde
X




Isovaleraldehyde oxime
X



P (Proline) Carbonyls
X




Glutamic-semialdehyde

X X


Pyroglutamic acid

X X


2-Pyrrolidone

X X


Hydroperoxides (unstable)
X




Alcohols
X




5-Hydroxy-2-aminovaleric acid
X




4-Hydroxyproline

X X


5-Hydroxyproline

X X

V (Valine) Carbonyls
X




Hydroxyperoxides (unstable)
X




Alcohols
X



C (Cysteine) Sulfenic acid

X



Sulfonamides
X




Cysteic acid
X
X


Sulfenyl chloride (unstable; from HOCl)
X




Cystin (disulfid; -S-S- bond) X
X X


Thiyl radicals X




M (Methionine) Methionine sulfoxide X X
X


Methionine sulfone X X
X

H (Histidine) Carbonyls (from O2)

X



2-Oxohistidine X X X X


Hydroperoxides (unstable; from O2)

X



Alcohols (from O2)

X



Chlorinated materials (unstable; from HOCl)

X



Aspartic acid X

X


Asparagine X

X

L (Lysine) Carbonyls
X




2-Amino-adipic-semialdehyde

X X


Hydroperoxides (unstable)
X




Alcohols
X




Chloramines (unstable; from HOCl)
X




Bromamines (unstable; from HOBr)
X



R (Arginine) Carbonyls
X




Glutamic-semialdehyde

X X


Hydroperoxides (unstable)
X




5-Hydroxy-2-aminovaleric acid
X




Chloramines (unstable; from HOCl)
X




Bromamines (unstable; from HOBr)
X



E (Glutamyl) Hydroperoxides (unstable)
X




Oxalic acid


X


Pyruvic acid


X

F (Phenylalanine) 2,3-Dihydroxyphenylalanine


X


2-Hydroxyphenylalanine (ortho-tyrosine) X X
X


3-Hydroxyphenylalanine (meta-tyrosine) X X
X


4-Hydroxyphenylalanine (tyrosine)
X
X


Nitrophenylalanine X




W (Typtophan) Alcohols and cyclized products (from O2)
X




Hydroperoxides (unstable; from O2)
X




2-Hydroxytryptophan X

X


4-Hydroxytryptophan X

X


5-Hydroxytryptophan X X
X


6-Hydroxytryptophan X

X


7-Hydroxytryptophan X X
X


Nitrotryptophan X

X


3-Hydroxykynurinine


X


N-Formylkynurenine X X
X


Kynurenine X X
X

Y (Tyrosine) Hydroperoxides (unstable; from O2)
X




Alcohols (from O2)
X




3,4-Dihydroxyphenylalanine (DOPA – unstable) X X
X


3-Nitrotyrosine X X




3-Chlorotyrosine, X X




3,5-Dichlorotyrosine X X




3-Bromotyrosine X X




3,5-Dibromotyrosine X X




Dityrosine (carbon-carbon dimer,
carbon-oxygen dimer, and higher species)
X





Tyrosine-tyrosine cross-linkages


X


Tyr-O-Tyr


X


Cross-linked nitrotyrosine


X


Cyclized products (from O2)
X



T (Threonine) 2-Amino-3-keto butyric acid

X X


References:

Fichtner M, Schuster S & Stark H (2021) Influence of spatial structure on protein damage susceptibility: a bioinformatics approach. Sci Rep 11, 4938. DOI:10.1038/s41598-021-84061-8 / EISSN:2045-2322

Fichtner M, Schuster S & Stark H (2021) Data for: Influence of spatial structure on protein damage susceptibility—A bioinformatics approach. Mendeley Data, Licence: CC BY 4.0. DOI:10.17632/jkmbpfgp4k.1

Fichtner M, Schuster S & Stark H (2020) Determination of scoring functions for protein damage susceptibility. Biosystems 187: 104035. DOI:10.1016/J.BIOSYSTEMS.2019.104035 / ISSN:0303-2647

Fichtner M, Schuster S & Stark H (2019) Data for: Determination of scoring functions for protein damage susceptibility. Mendeley Data, Licence: CC BY 4.0. DOI:10.17632/b2cbxsnvcx.1