Send to

Choose Destination
Protein Eng Des Sel. 2010 Nov;23(11):859-69. doi: 10.1093/protein/gzq062. Epub 2010 Sep 27.

Detecting subtle functional differences in ketopantoate reductase and related enzymes using a rule-based approach with sequence-structure homology recognition scores.

Author information

National Institute of Biomedical Innovation, 7-6-8 Saito-Asagi, Ibaraki, Osaka, Japan.


Ketopatoate reductase (KPR) is the second enzyme in the pantothenate (vitamin B(5)) biosynthesis pathway, an essential metabolic pathway identified as a potential target for new antimicrobials. The sequence similarity among putative KPRs is limited and KPR itself belongs to a large superfamily of 6-phosphogluconate dehydrogenases. Therefore, it is necessary to discriminate between true and other enzymes. In this paper, we describe a systematic analysis of putative KPRs in the context of this superfamily. Detailed structural analysis allowed us to define key residues for KPR activity and we classified eight structural genomics structures of the KPR family into four functional subclasses. We proposed a semi-automatic protocol, using sequence-structure homology recognition scores, for assigning KPR and related proteins to these subclasses and applied it to a representative set of 103 completely sequenced bacterial genomes. A similar approach can be applied to other enzyme families, which would aid the correct identification of drug targets and help design novel specific inhibitors.

[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Silverchair Information Systems
Loading ...
Support Center