1nho

From Proteopedia

Revision as of 10:57, 20 March 2008

Structural and Functional characterization of a Thioredoxin-like Protein from Methanobacterium thermoautotrophicum

Overview

Mt0807 is an 85-residue thiol-redox protein from the anaerobic archaebacterium Methanobacterium thermoautotrophicum. Its small size, its participation in certain redox reactions, and the presence of a "classic" glutareodoxin active-site sequence have led to the suggestion that it might be a glutaredoxin. However, studies by previous workers indicated that it exhibited neither glutaredoxin-like nor thioredoxin-like properties. To clarify the true role of this protein and its structure/functional relationship with a paralogous thioredoxin (Mt0895, 28% sequence identity) and a recently characterized orthologous protein (Mj0307, 51% sequence identity), we undertook a series of biochemical and biophysical studies. Comparative enzymatic assays and thiol titration experiments were combined with NMR structural studies and detailed 3D structure comparisons. Structurally, our results show that Mt0807 has a glutaredoxin-like fold (central four-stranded beta-sheet core surrounded by two helices on one side and a third on the other). However, more detailed comparisons with other members of the thioredoxin superfamily indicate that Mt0807 actually has several key structural and active-site characteristics more common to a thioredoxin. Furthermore, biochemical tests show that Mt0807 actually behaves as true thioredoxin. Comparisons between Mt0807 and its paralogue, Mt0895, indicate these two archaebacterial thioredoxins share very similar folds, but exhibit very different activities and likely serve somewhat different roles. On the basis of its greater relative abundance and significantly stronger redox activity, we believe that Mt0807 is the primary thioredoxin for M. thermoautotrophicum, while Mt0895 plays a minor or supportive role. We also suggest that these two molecules (Mt0807 and Mt0895) may represent a group of ancient proteins that were ancestral to both thioredoxins and glutaredoxins.

About this Structure

1NHO is a Single protein structure of sequence from Methanothermobacter thermautotrophicus. Full crystallographic information is available from OCA.

Reference

Structural and functional characterization of a thioredoxin-like protein (Mt0807) from Methanobacterium thermoautotrophicum., Amegbey GY, Monzavi H, Habibi-Nazhad B, Bhattacharyya S, Wishart DS, Biochemistry. 2003 Jul 8;42(26):8001-10. PMID:12834352

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