Disulfide conformation and design at helix N-termini.

Proteins
S InduRaghavan Varadarajan

Abstract

To understand structural and thermodynamic features of disulfides within an alpha-helix, a non-redundant dataset comprising of 5025 polypeptide chains containing 2311 disulfides was examined. Thirty-five examples were found of intrahelical disulfides involving a CXXC motif between the N-Cap and third helical positions. GLY and PRO were the most common amino acids at positions 1 and 2, respectively. The N-Cap residue for disulfide bonded CXXC motifs had average (phi,psi) values of (-112 +/- 25.2 degrees , 106 +/- 25.4 degrees ). To further explore conformational requirements for intrahelical disulfides, CYS pairs were introduced at positions N-Cap-3; 1,4; 7,10 in two helices of an Escherichia coli thioredoxin mutant lacking its active site disulfide (nSS Trx). In both helices, disulfides formed spontaneously during purification only at positions N-Cap-3. Mutant stabilities were characterized by chemical denaturation studies (in both oxidized and reduced states) and differential scanning calorimetry (oxidized state only). All oxidized as well as reduced mutants were destabilized relative to nSS Trx. All mutants were redox active, but showed decreased activity relative to wild-type thioredoxin. Such engineered disulfides can be us...Continue Reading

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Citations

Apr 25, 2013·Journal of Computer-aided Molecular Design·Rameshwar PrajapatiAbhay T Sangamwar
Sep 22, 2015·Frontiers in Immunology·Kristine N BrazinEllis L Reinherz
Mar 30, 2019·Chemical Biology & Drug Design·Ashwini DolleKonkallu Hanumae Gowd
Mar 16, 2019·Journal of Peptide Science : an Official Publication of the European Peptide Society·Craig A Bayse, Deanna B Pollard
Aug 21, 2020·Journal of Virology·Raksha DasRaghavan Varadarajan

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Methods Mentioned

BETA
circular dichroism
acetylation
light scattering

Software Mentioned

MODIP
SWISS
GROMACS
PDB Viewer
Origin
PSIPRED

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