Conservation of the PTEN catalytic motif in the bacterial undecaprenyl pyrophosphate phosphatase, BacA/UppP

J. S. Bickford, H. S. Nick
2013 Microbiology  
Isoprenoid lipid carriers are essential in protein glycosylation and bacterial cell envelope biosynthesis. The enzymes involved in their metabolism (synthases, kinases and phosphatases) are therefore critical to cell viability. In this review, we focus on two broad groups of isoprenoid pyrophosphate phosphatases. One group, containing phosphatidic acid phosphatase motifs, includes the eukaryotic dolichyl pyrophosphate phosphatases and proposed recycling bacterial undecaprenol pyrophosphate
more » ... hatases, PgpB, YbjB and YeiU/LpxT. The second group comprises the bacterial undecaprenol pyrophosphate phosphatase, BacA/UppP, responsible for initial formation of undecaprenyl phosphate, which we predict contains a tyrosine phosphate phosphatase motif resembling that of the tumour suppressor, phosphatase and tensin homologue (PTEN). Based on protein sequence alignments across species and 2D structure predictions, we propose catalytic and lipid recognition motifs unique to BacA/UppP enzymes. The verification of our proposed active-site residues would provide new strategies for the development of substratespecific inhibitors which mimic both the lipid and pyrophosphate moieties, leading to the development of novel antimicrobial agents. Abbreviations: CDG, congenital disorder of glycosylation; DHDDS, dehydrodolichyl diphosphate synthase; DK, dolichol kinase; DMAPP, dimethylallyl diphosphate; DOLPP1, dolichyl pyrophosphate phosphatase; Dol-P, dolichyl phosphate; Dol-PP, dolichyl pyrophosphate; DOXP, 1deoxy-D-xylulose 5-phosphate; DUSP, dual-specificity phosphatase; ER, endoplasmic reticulum; FPP, farnesyl pyrophosphate; IPP, isopentenyl pyrophosphate; MEP, 2C-methyl-D-erythritol 4-phosphate; PAP, phosphatidic acid phosphatase; PGP, phosphatidylglycerol phosphate; PTEN, phosphatase and tensin homologue; PTP, protein tyrosine phosphate.
doi:10.1099/mic.0.070474-0 pmid:24068241 fatcat:5ub4x3wki5eihgf4khj7d677ay