Conformational changes in redox pairs of protein structures.
Disulfides are conventionally viewed as structurally stabilizing elements in proteins but emerging evidence suggests two disulfide subproteomes exist. One group mediates the well known role of structural stabilization. A second redox-active group are best known for their catalytic functions but are increasingly being recognized for their roles in regulation of protein function. Redox-active disulfides are, by their very nature, more susceptible to reduction than structural disulfides; and conversely, the Cys pairs that form them are more susceptible to oxidation. In this study, we searched for potentially redox-active Cys Pairs by scanning the Protein Data Bank for structures of proteins in alternate redox states. The PDB contains over 1134 unique redox pairs of proteins, many of which exhibit conformational differences between alternate redox states. Several classes of structural changes were observed, proteins that exhibit: disulfide oxidation following expulsion of metals such as zinc; major reorganisation of the polypeptide backbone in association with disulfide redox-activity; order/disorder transitions; and changes in quaternary structure. Based on evidence gathered supporting disulfide redox activity, we propose disulfides present in alternate redox states are likely to have physiologically relevant redox activity.
Fan
Samuel W
SW
Structural and Computational Biology Program, Victor Chang Cardiac Research Institute, Darlinghurst, New South Wales 2010, Australia.
George
Richard A
RA
Haworth
Naomi L
NL
Feng
Lina L
LL
Liu
Jason Y
JY
Wouters
Merridee A
MA
D019295:Computational Biology; D030562:Databases, Protein; D004220:Disulfides / Q000737:chemistry / Q000378:metabolism*; D008670:Metals / Q000378:metabolism*; D010084:Oxidation-Reduction; D011487:Protein Conformation; D017434:Protein Structure, Tertiary / Q000502:physiology; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism
D004220:Disulfides; D008670:Metals; D011506:Proteins