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Protein disulfides with peroxiredoxin IV and PDI peroxidases

Published on: Author: Colin Thorpe

Two distinct types of flavin-linked oxidases catalyze the generation of protein disulfide bonds in the secretory apparatus of mammals.  The Ero1α and – β isoforms oxidize protein disulfide isomerases (PDI) leading to the net generation of disulfide bonds as shown in Figure A.  Here, PDI is the immediate oxidant for unfolded reduced proteins. In contrast,… Continue reading

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A human mitochondrial sulfhydryl oxidase mutant characterized

Published on: Author: Colin Thorpe

In 2009, Comi and coworkers (Di Fonzo et al., PubMed) identified the point mutation that caused three children of consanguineous parents to develop cataract, progressive muscle weakness, hearing loss and developmental delay.  The mutant protein was a mitochondrial sulfhydryl oxidase: augmenter of liver regeneration (here abbreviated ALR).  The long form of ALR is resident in… Continue reading

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QSOX – a structural puzzle solved

Published on: Author: Colin Thorpe

Depending on the source, QSOX sequences start with one or two thioredoxin domains (the bar diagram is for metazoans).  The remaining two domains are common to all QSOXs: a helix-rich region (HRR) and a flavin-binding domain (Erv/ALR, yellow).  The latter is the engine of QSOX catalysis – driving the generation of disulfide bonds and reducing… Continue reading

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An enzymological malapropism – oxidoreductase not “oxidase”!

Published on: Author: Colin Thorpe

The activity that came to be named protein disulfide isomerase (PDI) was uncovered independently by Straub and Anfinsen in 1963.  PDI was assigned an enzyme classification number (EC 5.3.4.1) in 1972: EC 5…        corresponds to “isomerase” EC 5.3…     corresponds to “intramolecular oxidoreductases” EC 5.3.4.    designation is for the category “transposing S-S bonds”. So PDI is… Continue reading

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Prostate cancer and the expression of QSOX1

Published on: Author: Colin Thorpe

A recent paper:  Loss of Nkx3.1 leads to the activation of discrete downstream target genes during prostate tumorigenesis. Oncogene. 2009 Sep 17;28(37):3307-19. Epub 2009 Jul 13 [PubMed] Song H, Zhang B, Watson MA, Humphrey PA, Lim H, Milbrandt J. Song et al. have shown that loss of the androgen-regulated transcriptional regulator NKX3.1 leads to over-expression… Continue reading

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NOTCH: Ero1L and QSOX3

Published on: Author: Colin Thorpe

NOTCH signaling in Drosophila: disulfide bonds introduced by both Ero1L and QSOX3! The paper:  Ero1L, a thiol oxidase, is required for Notch signaling through cysteine bridge formation of the Lin12-Notch repeats in Drosophila melanogaster. Tien AC, Rajan A, Schulze KL, Ryoo HD, Acar M, Steller H, Bellen HJ. J Cell Biol. 2008 Sep 22;182(6):1113-25. [Link… Continue reading

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