Linear array of conserved sequence motifs to discriminate protein subfamilies: study on pyridine nucleotide-disulfide reductases.
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.


CONCLUSIONS
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.
Avila
César L
CL
Departamento Bioquímica de la Nutrición, Instituto Superior de Investigaciones Biológicas (CONICET-UNT), San Miguel de Tucumán, Tucumán, Argentina. cavila@fbqf.unt.edu.ar <cavila@fbqf.unt.edu.ar>
Rapisarda
Viviana A
VA
Farías
Ricardo N
RN
De Las Rivas
Javier
J
Chehín
Rosana
R
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D003198:Computer Simulation; D017124:Conserved Sequence; D016002:Discriminant Analysis; D004220:Disulfides / Q000737:chemistry; D016014:Linear Models; D008956:Models, Chemical; D008969:Molecular Sequence Data; D009711:Nucleotides / Q000737:chemistry; D010088:Oxidoreductases / Q000737:chemistry* / Q000145:classification; D011725:Pyridines / Q000737:chemistry*; D016415:Sequence Alignment / Q000379:methods*; D020539:Sequence Analysis, Protein / Q000379:methods*; D017386:Sequence Homology, Amino Acid
D004220:Disulfides; D009711:Nucleotides; D011725:Pyridines; D010088:Oxidoreductases; C023666:pyridine