1OC8

TRYPAREDOXIN II FROM C.FASCICULATA SOLVED BY MR

Summary for 1OC8

• Entry DOI: 10.2210/pdb1oc8/pdb
• Related: 1EWX 1EZK 1FG4 1I5G 1O6J 1O73 1O7U 1O81 1O85 1O8W 1O8X 1OC9 1QK8
• Descriptor: TRYPAREDOXIN II, SULFATE ION (3 entities in total)
• Functional Keywords: electron transport, tryparedoxin ii
• Biological source: CRITHIDIA FASCICULATA
• Total number of polymer chains: 2
• Total formula weight: 34423.51

Authors

Leonard, G.A.,Micossi, E.,Hunter, W.N. (deposition date: 2003-02-07, release date: 2003-04-02, Last modification date: 2023-12-13)

Primary citation

Alphey, M.S.,Gabrielsen, M.,Micossi, E.,Leonard, G.A.,Mcsweeney, S.M.,Ravelli, R.B.G.,Tetaud, E.,Fairlamb, A.H.,Bond, C.S.,Hunter, W.N.
Tryparedoxins from Crithidia Fasciculata and Trypanosoma Brucei: Photoreduction of the Redox Disulfide Using Synchrotron Radiation and Evidence for a Conformational Switch Implicated in Function
J.Biol.Chem., 278:25919-, 2003

PubMed Abstract: Tryparedoxin (TryX) is a member of the thioredoxin (TrX) fold family involved in the regulation of oxidative stress in parasitic trypanosomatids. Like TrX, TryX carries a characteristic Trp-Cys-Xaa-Xaa-Cys motif, which positions a redox-active disulfide underneath a tryptophan lid. We report the structure of a Crithidia fasciculata tryparedoxin isoform (CfTryX2) in two crystal forms and compare them with structures determined previously. Efforts to chemically generate crystals of reduced TryX1 were unsuccessful, and we carried out a novel experiment to break the redox-active disulfide, formed between Cys-40 and Cys-43, utilizing the intense x-radiation from a third generation synchrotron undulator beamline. A time course study of the S-S bond cleavage is reported with the structure of a TryX1 C43A mutant as the control. When freed from the constraints of a disulfide link to Cys-43, Cys-40 pivots to become slightly more solvent-accessible. In addition, we have determined the structure of Trypanosoma brucei TryX, which, influenced by the molecular packing in the crystal lattice, displays a significantly different orientation of the active site tryptophan lid. This structural change may be of functional significance when TryX interacts with tryparedoxin peroxidase, the final protein in the trypanothione-dependent peroxidase pathway. Comparisons with chloroplast TrX and its substrate fructose 1,6-bisphosphate phosphatase suggest that this movement may represent a general feature of redox regulation in the trypanothione and thioredoxin peroxidase pathways.

PubMed: 12707277
DOI: 10.1074/JBC.M301526200

Experimental method

X-RAY DIFFRACTION (1.5 Å)