4HS1

High-resolution crystal structure of Glutaredoxin like protein NrdH from Mycobacterium tuberculosis.

4HS1 の概要

• エントリーDOI: 10.2210/pdb4hs1/pdb
• 分子名称: Glutaredoxin NrdH, putative, NITRATE ION, CHLORIDE ION, ... (6 entities in total)
• 機能のキーワード: thioredoxin, glutaredoxin like, thioredoxin reductase, cytosol, electron transport
• 由来する生物種: Mycobacterium tuberculosis
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 9614.20

構造登録者

Phulera, S.,Mande, S.C. (登録日: 2012-10-29, 公開日: 2013-06-26, 最終更新日: 2024-11-20)

主引用文献

Phulera, S.,Mande, S.C.
The Crystal Structure of Mycobacterium tuberculosis NrdH at 0.87 A Suggests a Possible Mode of Its Activity.
Biochemistry, 52:4056-4065, 2013

PubMed Abstract: Members of the NrdH family of redox proteins, which consists of small glutaredoxin-like proteins with thioredoxin-like activity, serve as the reducing partners of class Ib ribonucleotide reductases. Here, we report the crystal structure of NrdH from Mycobacterium tuberculosis, refined to a crystallographic R factor of 14.02% (Rfree = 15.53%) at 0.87 Å resolution. The tertiary structure of M. tuberculosis NrdH has a typical thioredoxin fold as expected. The extremely high resolution of the structure allows us to dissect the functionality of the protein in great depth. Structural superimposition of M. tuberculosis NrdH and thioredoxin reductase over the Escherichia coli thioredoxin reductase-thioredoxin complex suggests the ability of NrdH to accept electrons from M. tuberculosis thioredoxin reductase. This raises the important question of why glutaredoxins are unable to accept electrons from thioredoxin reductases and why thioredoxins are unable to reduce ribonucleotide reductases. Furthermore, forms of NrdH from other organisms have been shown to be a specific reductant of class Ib ribonucleotide reductases. We attempt to explain this substrate specificity by modeling the C-terminal peptide of a ribunucleotide subunit, NrdE, in the active site of NrdH using the already available Grx-NrdA-Cter-peptide structure. Statistical coupling analysis of NrdH, glutaredoxins, and thioredoxins reveals different sets of co-evolving contiguous clusters of amino acid residues, which might explain the differences in the biochemical properties of these structurally similar yet functionally distinct subclasses of proteins.

PubMed: 23675692
DOI: 10.1021/bi400191z

実験手法

X-RAY DIFFRACTION (0.87 Å)