6IJB

Structure of 3-methylmercaptopropionate CoA ligase mutant K523A in complex with AMP and MMPA

Summary for 6IJB

• Entry DOI: 10.2210/pdb6ijb/pdb
• Descriptor: AMP-binding domain protein, ADENOSINE MONOPHOSPHATE, 2-[3-(2-HYDROXY-1,1-DIHYDROXYMETHYL-ETHYLAMINO)-PROPYLAMINO]-2-HYDROXYMETHYL-PROPANE-1,3-DIOL, ... (5 entities in total)
• Functional Keywords: coa ligase, atp dependent, comformational change, ligase
• Biological source: Ruegeria lacuscaerulensis (strain DSM 11314 / KCTC 2953 / ITI-1157) (Silicibacter lacuscaerulensis)
• Total number of polymer chains: 2
• Total formula weight: 119564.47

Authors

Shao, X.,Cao, H.Y.,Wang, P.,Li, C.Y.,Zhao, F.,Peng, M.,Chen, X.L.,Zhang, Y.Z. (deposition date: 2018-10-09, release date: 2019-07-03, Last modification date: 2023-11-22)

Primary citation

Shao, X.,Cao, H.Y.,Zhao, F.,Peng, M.,Wang, P.,Li, C.Y.,Shi, W.L.,Wei, T.D.,Yuan, Z.,Zhang, X.H.,Chen, X.L.,Todd, J.D.,Zhang, Y.Z.
Mechanistic insight into 3-methylmercaptopropionate metabolism and kinetical regulation of demethylation pathway in marine dimethylsulfoniopropionate-catabolizing bacteria.
Mol.Microbiol., 111:1057-1073, 2019

PubMed Abstract: The vast majority of oceanic dimethylsulfoniopropionate (DMSP) is thought to be catabolized by bacteria via the DMSP demethylation pathway. This pathway contains four enzymes termed DmdA, DmdB, DmdC and DmdD/AcuH, which together catabolize DMSP to acetylaldehyde and methanethiol as carbon and sulfur sources respectively. While molecular mechanisms for DmdA and DmdD have been proposed, little is known of the catalytic mechanisms of DmdB and DmdC, which are central to this pathway. Here, we undertake physiological, structural and biochemical analyses to elucidate the catalytic mechanisms of DmdB and DmdC. DmdB, a 3-methylmercaptopropionate (MMPA)-coenzyme A (CoA) ligase, undergoes two sequential conformational changes to catalyze the ligation of MMPA and CoA. DmdC, a MMPA-CoA dehydrogenase, catalyzes the dehydrogenation of MMPA-CoA to generate MTA-CoA with Glu435 as the catalytic base. Sequence alignment suggests that the proposed catalytic mechanisms of DmdB and DmdC are likely widely adopted by bacteria using the DMSP demethylation pathway. Analysis of the substrate affinities of involved enzymes indicates that Roseobacters kinetically regulate the DMSP demethylation pathway to ensure DMSP functioning and catabolism in their cells. Altogether, this study sheds novel lights on the catalytic and regulative mechanisms of bacterial DMSP demethylation, leading to a better understanding of bacterial DMSP catabolism.

PubMed: 30677184
DOI: 10.1111/mmi.14211

Experimental method

X-RAY DIFFRACTION (2.111 Å)