7OCP

NADPH bound to the dehydrogenase domain of the bifunctional mannitol-1-phosphate dehydrogenase/phosphatase MtlD from Acinetobacter baumannii

Summary for 7OCP

• Entry DOI: 10.2210/pdb7ocp/pdb
• Descriptor: HAD hydrolase, family IA, variant 3, 1,2-ETHANEDIOL, MAGNESIUM ION, ... (8 entities in total)
• Functional Keywords: mannitol, dehydrogenase, phosphatase, nadph, fructose-6-phosphate, oxidoreductase, had hydrolase family ia variant 3
• Biological source: Acinetobacter baumannii (strain ATCC 19606 / DSM 30007 / CIP 70.34 / JCM 6841 / NBRC 109757 / NCIMB 12457 / NCTC 12156 / 81)
• Total number of polymer chains: 2
• Total formula weight: 169295.44

Authors

Tam, H.K.,Mueller, V.,Pos, K.M. (deposition date: 2021-04-28, release date: 2022-04-20, Last modification date: 2024-01-31)

Primary citation

Tam, H.K.,Konig, P.,Himpich, S.,Ngu, N.D.,Abele, R.,Muller, V.,Pos, K.M.
Unidirectional mannitol synthesis of Acinetobacter baumannii MtlD is facilitated by the helix-loop-helix-mediated dimer formation.
Proc.Natl.Acad.Sci.USA, 119:e2107994119-e2107994119, 2022

PubMed Abstract: Persistence of Acinetobacter baumannii in environments with low water activity is largely attributed to the biosynthesis of compatible solutes. Mannitol is one of the key compatible solutes in A. baumannii, and it is synthesized by a bifunctional mannitol-1-phosphate dehydrogenase/phosphatase (AbMtlD). AbMtlD catalyzes the conversion of fructose-6-phosphate to mannitol in two consecutive steps. Here, we report the crystal structure of dimeric AbMtlD, constituting two protomers each with a dehydrogenase and phosphatase domain. A proper assembly of AbMtlD dimer is facilitated by an intersection comprising a unique helix–loop–helix (HLH) domain. Reduction and dephosphorylation catalysis of fructose-6-phosphate to mannitol is dependent on the transient dimerization of AbMtlD. AbMtlD presents as a monomer under lower ionic strength conditions and was found to be mainly dimeric under high-salt conditions. The AbMtlD catalytic efficiency was markedly increased by cross-linking the protomers at the intersected HLH domain via engineered disulfide bonds. Inactivation of the AbMtlD phosphatase domain results in an intracellular accumulation of mannitol-1-phosphate in A. baumannii, leading to bacterial growth impairment upon salt stress. Taken together, our findings demonstrate that salt-induced dimerization of the bifunctional AbMtlD increases catalytic dehydrogenase and phosphatase efficiency, resulting in unidirectional catalysis of mannitol production.

PubMed: 35363566
DOI: 10.1073/pnas.2107994119

Experimental method

X-RAY DIFFRACTION (2.75 Å)