Canavan Task 6 - Sequence-based mutation analysis

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Revision as of 14:29, 13 June 2012 by Gatzmannf (talk | contribs) (Physico-chemical effects)

Protocol

Further information can be found in the protocol.

Choosing mutations

mutant E285A A305E G123E R71H R71C K213E V278M A93A T277T P280P
known effect 1% activity in Ashkenazi Jews 0% activity in non-Ashkenazi 25% Canavan Disease not disease related Canavan Disease not disease related synonymous SNPs - not disease related synonymous SNPs - not disease related synonymous SNPs - not disease related
structural location helix - binding pocket loop C-terminus beta-sheet active site active site loop region loop region outer helix outer loop outer loop

Physico-chemical effects

Hydrophobicity: Kyte J, Doolittle RF (May 1982).Journal of Molecular Biology 157 (1): 105–32.
Volume: A.A. Zamyatin, Prog. Biophys. Mol. Biol., 24(1972)107-123
Pi: JC Biro, Theor Biol Med Model. 2006; 3: 15
Grantham Score: Grantham R (1974) Amino acid difference formula to help explain protein evolution. Science 185: 862–864
mutation Amino acid Hydrophobicity (and diff.) Volume [Å3] (and diff.) Isoelectric point pI(Charge) Grantham Score
E285A glutamic acid -3.5 (polar) 5.3 138.4 (bulky) 49.8 3.2 (negative) 2.8 107
alanine 1.8 (nonpolar) 88.6 (tiny) 6.0 (neutral)
A305E alanine 1.8 (nonpolar) 5.3 88.6 (tiny) 49.8 6.0 (neutral) 2.8 107
glutamic acid -3.5 (polar) 138.4 (bulky) 3.2 (negative)
G123E Glycine -0.4 (nonpolar) 3.1 60.1 (tiny) 78.3 6.0 (neutral) 2.8 98
glutamic acid -3.5 (polar) 138.4 (bulky) 3.2 (negative)
R71H Arginine -4.5 (polar) 1.3 173.4 (bulky) 20.2 10.8 (positive) 3.2 29
Histidine -3.2 (polar) 153.2 (bulky) 7.6 (neutral)
R71H Arginine -4.5 (polar) 1.3 173.4 (bulky) 20.2 10.8 (positive) 3.2 29
Histidine -3.2 (polar) 153.2 (bulky) 7.6 (neutral)


conservative (0-50), moderately conservative (51-100), moderately radical (101-150), or radical (≥151) according to the classification proposed by