1hh8: Difference between revisions
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==Overview== | ==Overview== | ||
Upon activation, the NADPH oxidase from neutrophils produces superoxide, anions in response to microbial infection. This enzymatic complex is, activated by association of its cytosolic factors p67(phox), p47(phox), and the small G protein Rac with a membrane-associated flavocytochrome, b(558). Here we report the crystal structure of the active N-terminal, fragment of p67(phox) at 1.8 A resolution, as well as functional studies, of p67(phox) mutants. This N-terminal region (residues 1-213) consists, mainly of four TPR (tetratricopeptide repeat) motifs in which the C, terminus folds back into a hydrophobic groove formed by the TPR domain., The structure is very similar to that of the inactive truncated form of, p67(phox) bound to the small G protein Rac previously reported, but, differs by ... | Upon activation, the NADPH oxidase from neutrophils produces superoxide, anions in response to microbial infection. This enzymatic complex is, activated by association of its cytosolic factors p67(phox), p47(phox), and the small G protein Rac with a membrane-associated flavocytochrome, b(558). Here we report the crystal structure of the active N-terminal, fragment of p67(phox) at 1.8 A resolution, as well as functional studies, of p67(phox) mutants. This N-terminal region (residues 1-213) consists, mainly of four TPR (tetratricopeptide repeat) motifs in which the C, terminus folds back into a hydrophobic groove formed by the TPR domain., The structure is very similar to that of the inactive truncated form of, p67(phox) bound to the small G protein Rac previously reported, but, differs by the presence of a short C-terminal helix (residues 187-193), that might be part of the activation domain. All p67(phox) mutants, responsible for Chronic Granulomatous Disease (CGD), a severe defect of, NADPH oxidase function, are localized in the N-terminal region. We, investigated two CGD mutations, G78E and A128V. Surprisingly, the A128V, CGD mutant is able to fully activate the NADPH oxidase in vitro at 25, degrees C. However, this point mutation represents a temperature-sensitive, defect in p67(phox) that explains its phenotype at physiological, temperature. | ||
==About this Structure== | ==About this Structure== | ||
1HH8 is a | 1HH8 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with FLC as [http://en.wikipedia.org/wiki/ligand ligand]. Structure known Active Site: FLC. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1HH8 OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: tpr repeat]] | [[Category: tpr repeat]] | ||
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Revision as of 14:35, 5 November 2007
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THE ACTIVE N-TERMINAL REGION OF P67PHOX: STRUCTURE AT 1.8 ANGSTROM RESOLUTION AND BIOCHEMICAL CHARACTERIZATIONS OF THE A128V MUTANT IMPLICATED IN CHRONIC GRANULOMATOUS DISEASE
OverviewOverview
Upon activation, the NADPH oxidase from neutrophils produces superoxide, anions in response to microbial infection. This enzymatic complex is, activated by association of its cytosolic factors p67(phox), p47(phox), and the small G protein Rac with a membrane-associated flavocytochrome, b(558). Here we report the crystal structure of the active N-terminal, fragment of p67(phox) at 1.8 A resolution, as well as functional studies, of p67(phox) mutants. This N-terminal region (residues 1-213) consists, mainly of four TPR (tetratricopeptide repeat) motifs in which the C, terminus folds back into a hydrophobic groove formed by the TPR domain., The structure is very similar to that of the inactive truncated form of, p67(phox) bound to the small G protein Rac previously reported, but, differs by the presence of a short C-terminal helix (residues 187-193), that might be part of the activation domain. All p67(phox) mutants, responsible for Chronic Granulomatous Disease (CGD), a severe defect of, NADPH oxidase function, are localized in the N-terminal region. We, investigated two CGD mutations, G78E and A128V. Surprisingly, the A128V, CGD mutant is able to fully activate the NADPH oxidase in vitro at 25, degrees C. However, this point mutation represents a temperature-sensitive, defect in p67(phox) that explains its phenotype at physiological, temperature.
About this StructureAbout this Structure
1HH8 is a Single protein structure of sequence from Homo sapiens with FLC as ligand. Structure known Active Site: FLC. Full crystallographic information is available from OCA.
ReferenceReference
The active N-terminal region of p67phox. Structure at 1.8 A resolution and biochemical characterizations of the A128V mutant implicated in chronic granulomatous disease., Grizot S, Fieschi F, Dagher MC, Pebay-Peyroula E, J Biol Chem. 2001 Jun 15;276(24):21627-31. Epub 2001 Mar 21. PMID:11262407
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