Molecular evolutionary and structural analysis of human UCHL1 gene demonstrates the relevant role of intragenic epistasis in Parkinson’s disease and other neurological disorders

Table 3 Structural comparisons of disease causing mutant versions of UCHL1 protein

Mutations	Major changes in residue number	Major shifts in region	Critical region
Ile93Met	23–24	C12-peptidase Domain	32–39 (Secretion, Signal Motif)
	32–38	Secretion signal Motif
	45,74–75
	136,148
	222–223	Farnesylation site
Glu7Ala	22–25	C12- peptidase Domain	32–39(Secretion, Signal Motif)
	31–38	Secretion signal Motif
	45,74–75
	111–112
	190–191,136	CK2 Phosphorylation site
Ser18Tyr	23–25,	C12 peptidase Domain	32–39 (Secretion, Signal Motif)
	31–38,	Secretion signal Motif
	45,74–75
	111–112
	150–152
	148,136
	222–223	Farnesylation site
Arg178Gln	23–24	C12-peptidase Domain	32–39(Secretion, Signal Motif
	32–39	Secretion signal Motif
	136,74
	221–223	Farnesylation site
Ala216Asp	23–24	C12-peptidase Domain
	74–75		___
	136,148
	222–223	Farnesylation site

This table shows the impact of PD (Parkinson’s disease) and other neurological disorders causing missense mutations on backbone torsion angles of human UCHL1 protein. In the first column, amino acid residue on the left indicates the wild-type residue, whereas the residue on the right is mutated version; number indicates the amino acid position. The second column specifies the positions at which major structural deviations are observed. The third column depicts the deviated region. The fourth column depicts deviated residues shared among all mutant structures of UCHL1 protein

ISSN: 2730-7182