Structural highlights
Function
[RPFE_MYCTU] Factor that stimulates resuscitation of dormant cells. Has peptidoglycan (PG) hydrolytic activity. Active in the pM concentration range. Has little to no effect on actively-growing cells. PG fragments could either directly activate the resuscitation pathway of dormant bacteria or serve as a substrate for endogenous Rpf, resulting in low molecular weight products with resuscitation activity.[1] Stimulates growth of stationary phase M.bovis (a slow-growing Mycobacterium), reduces the lag phase of diluted fast-growers M.smegmatis and Micrococcus luteus. Sequential gene disruption indicates RpfB and RpfE are higher than RpfD and RpfC in functional hierarchy.[2]
Publication Abstract from PubMed
Resuscitation promoting factor (Rpf) proteins, which hydrolyze the sugar chains in cell-wall peptidoglycan (PG), play key roles in prokaryotic cell elongation, division and escape from dormancy to vegetative growth. Like other bacteria, Mycobacterium tuberculosis (Mtb) expresses multiple Rpfs, none of which is individually essential. This redundancy has left unclear the distinct functions of the different Rpfs. To explore the distinguishing characteristics of the five Mtb Rpfs, we determined the crystal structure of the RpfE catalytic domain. The protein adopts the characteristic Rpf fold, but the catalytic cleft is narrower compared to Mtb RpfB. Also in contrast to RpfB, in which the substrate-binding surfaces are negatively charged, the corresponding RpfE catalytic pocket and predicted peptide-binding sites are more positively charged at neutral pH. The complete reversal of the electrostatic potential of the substrate-binding site suggests that the different Rpfs function optimally at different pHs or most efficiently hydrolyze different micro-domains of PG. These studies provide insights into the molecular determinants of the evolution of functional specialization in Rpfs.
Mycobacterium tuberculosis RpfE crystal structure reveals a positively charged catalytic cleft.,Mavrici D, Prigozhin DM, Alber T Protein Sci. 2014 Jan 22. doi: 10.1002/pro.2431. PMID:24452911[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Mukamolova GV, Turapov OA, Young DI, Kaprelyants AS, Kell DB, Young M. A family of autocrine growth factors in Mycobacterium tuberculosis. Mol Microbiol. 2002 Nov;46(3):623-35. PMID:12410821
- ↑ Mukamolova GV, Turapov OA, Young DI, Kaprelyants AS, Kell DB, Young M. A family of autocrine growth factors in Mycobacterium tuberculosis. Mol Microbiol. 2002 Nov;46(3):623-35. PMID:12410821
- ↑ Mavrici D, Prigozhin DM, Alber T. Mycobacterium tuberculosis RpfE crystal structure reveals a positively charged catalytic cleft. Protein Sci. 2014 Jan 22. doi: 10.1002/pro.2431. PMID:24452911 doi:http://dx.doi.org/10.1002/pro.2431
