4x1u
The structure of AhpE from Mycobacterium tuberculosis revisited
Structural highlights
FunctionAHPE_MYCTU Thiol-specific peroxidase that catalyzes the reduction of hydrogen peroxide and organic hydroperoxides to water and alcohols, respectively. Plays a role in cell protection against oxidative stress by detoxifying peroxides. May represent an important antioxidant defense against cytotoxic peroxides, especially peroxynitrite, which can be formed by activated macrophages during infection.[1] [2] Publication Abstract from PubMedIn many established methods, identification of hydrogen bonds (H-bonds) is primarily based on pairwise comparison of distances between atoms. These methods often give rise to systematic errors when sulfur is involved. A more accurate method is the non-covalent interaction index, which determines the strength of the H-bonds based on the associated electron density and its gradient. We applied the NCI index on the active site of a single-cysteine peroxiredoxin. We found a different sulfur hydrogen-bonding network to that typically found by established methods, and we propose a more accurate equation for determining sulfur H-bonds based on geometrical criteria. This new algorithm will be implemented in the next release of the widely-used CHARMM program (version 41b), and will be particularly useful for analyzing water molecule-mediated H-bonds involving different atom types. Furthermore, based on the identification of the weakest sulfur-water H-bond, the location of hydrogen peroxide for the nucleophilic attack by the cysteine sulfur can be predicted. In general, current methods to determine H-bonds will need to be reevaluated, thereby leading to better understanding of the catalytic mechanisms in which sulfur chemistry is involved. Revisiting sulfur H-bonds in proteins: The example of peroxiredoxin AhpE.,van Bergen LA, Alonso M, Pallo A, Nilsson L, De Proft F, Messens J Sci Rep. 2016 Jul 29;6:30369. doi: 10.1038/srep30369. PMID:27468924[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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