7QSJ

Methylmannose polysaccharide hydrolase MmpH from M. hassiacum

Summary for 7QSJ

• Entry DOI: 10.2210/pdb7qsj/pdb
• Descriptor: Methylmannose polysaccharide hydrolase (MmpH), MAGNESIUM ION, NICKEL (II) ION, ... (5 entities in total)
• Functional Keywords: methylmannose polysaccharide, hydrolase, mycobacterium hassiacum, endomannosidase
• Biological source: Mycolicibacterium hassiacum
• Total number of polymer chains: 2
• Total formula weight: 83174.72

Authors

Ripoll-Rozada, J.,Manso, J.A.,Pereira, P.J.B. (deposition date: 2022-01-13, release date: 2023-01-25, Last modification date: 2024-06-19)

Primary citation

Maranha, A.,Costa, M.,Ripoll-Rozada, J.,Manso, J.A.,Miranda, V.,Mendes, V.M.,Manadas, B.,Macedo-Ribeiro, S.,Ventura, M.R.,Pereira, P.J.B.,Empadinhas, N.
Self-recycling and partially conservative replication of mycobacterial methylmannose polysaccharides.
Commun Biol, 6:108-108, 2023

PubMed Abstract: The steep increase in nontuberculous mycobacteria (NTM) infections makes understanding their unique physiology an urgent health priority. NTM synthesize two polysaccharides proposed to modulate fatty acid metabolism: the ubiquitous 6-O-methylglucose lipopolysaccharide, and the 3-O-methylmannose polysaccharide (MMP) so far detected in rapidly growing mycobacteria. The recent identification of a unique MMP methyltransferase implicated the adjacent genes in MMP biosynthesis. We report a wide distribution of this gene cluster in NTM, including slowly growing mycobacteria such as Mycobacterium avium, which we reveal to produce MMP. Using a combination of MMP purification and chemoenzymatic syntheses of intermediates, we identified the biosynthetic mechanism of MMP, relying on two enzymes that we characterized biochemically and structurally: a previously undescribed α-endomannosidase that hydrolyses MMP into defined-sized mannoligosaccharides that prime the elongation of new daughter MMP chains by a rare α-(1→4)-mannosyltransferase. Therefore, MMP biogenesis occurs through a partially conservative replication mechanism, whose disruption affected mycobacterial growth rate at low temperature.

PubMed: 36707645
DOI: 10.1038/s42003-023-04448-3

Experimental method

X-RAY DIFFRACTION (1.35 Å)