1qk8
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(New page: 200px<br /><applet load="1qk8" size="450" color="white" frame="true" align="right" spinBox="true" caption="1qk8, resolution 1.4Å" /> '''TRYPAREDOXIN-I FROM C...)
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Revision as of 02:02, 25 November 2007
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TRYPAREDOXIN-I FROM CRITHIDIA FASCICULATA
Overview
Tryparedoxin-I is a recently discovered thiol-disulfide oxidoreductase, involved in the regulation of oxidative stress in parasitic, trypanosomatids. The crystal structure of recombinant Crithidia, fasciculata tryparedoxin-I in the oxidized state has been determined using, multi-wavelength anomalous dispersion methods applied to a selenomethionyl, derivative. The model comprises residues 3 to 145 with 236 water molecules, and has been refined using all data between a 19- and 1.4-A resolution to, an R-factor and R-free of 19.1 and 22.3%, respectively. Despite sharing, only about 20% sequence identity, tryparedoxin-I presents a five-stranded, twisted beta-sheet and two elements of helical structure in the same type, of fold as displayed by thioredoxin, the archetypal thiol-disulfide, oxidoreductase. However, the relationship of secondary structure with the, linear amino acid sequences is different for each protein, producing a, distinctive topology. The beta-sheet core is extended in the, trypanosomatid protein with an N-terminal beta-hairpin. There are also, differences in the content and orientation of helical elements of, secondary structure positioned at the surface of the proteins, which leads, to different shapes and charge distributions between human thioredoxin and, tryparedoxin-I. A right-handed redox-active disulfide is formed between, Cys-40 and Cys-43 at the N-terminal region of a distorted alpha-helix, (alpha1). Cys-40 is solvent-accessible, and Cys-43 is positioned in a, hydrophilic cavity. Three C-H...O hydrogen bonds donated from two proline, residues serve to stabilize the disulfide-carrying helix and support the, correct alignment of active site residues. The accurate model for, tryparedoxin-I allows for comparisons with the family of thiol-disulfide, oxidoreductases and provides a template for the discovery or design of, selective inhibitors of hydroperoxide metabolism in trypanosomes. Such, inhibitors are sought as potential therapies against a range of human, pathogens.
About this Structure
1QK8 is a Single protein structure of sequence from Crithidia fasciculata. Full crystallographic information is available from OCA.
Reference
The high resolution crystal structure of recombinant Crithidia fasciculata tryparedoxin-I., Alphey MS, Leonard GA, Gourley DG, Tetaud E, Fairlamb AH, Hunter WN, J Biol Chem. 1999 Sep 3;274(36):25613-22. PMID:10464297
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