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[Background]: The pyridine nucleotide disulfide reductase (PNDR) is a large and heterogeneous
protein family divided into two classes (I and II), which reflect the divergent evolution of its
characteristic disulfide redox active site. However, not all the PNDR members fit into these
categories and this suggests the need of further studies to achieve a more comprehensive
classification of this complex family.
[Results]: A workflow to improve the clusterization of protein families based on the array of linear
conserved motifs is designed. The method is applied to the PNDR large family finding two main
groups, which correspond to PNDR classes I and II. However, two other separate protein clusters,
previously classified as class I in most databases, are outgrouped: the peroxide reductases (NAOX,
NAPE) and the type II NADH dehydrogenases (NDH-2). In this way, two novel PNDR classes III
and IV for NAOX/NAPE and NDH-2 respectively are proposed. By knowledge-driven biochemical
and functional data analyses done on the new class IV, a linear array of motifs putatively related to
Cu(II)-reductase activity is detected in a specific subset of NDH-2.
[Conclusion]: The results presented are a novel contribution to the classification of the complex
and large PNDR protein family, supporting its reclusterization into four classes. The linear array of
motifs detected within the class IV PNDR subfamily could be useful as a signature for a particular
subgroup of NDH-2.
This research was supported by grants PIP 6399 from Consejo Nacional de
Investigaciones Científicas y Técnicas (CONICET), PICT 22221 from Agencia
Nacional de Promoción Científica y Tecnológica (ANPCyT), and 26/D-313 from Secretaría de Ciencia y Técnica de la Universidad Nacional de
Tucumán (CIUNT) all in Argentina.
Peer reviewed