5cx7
From Proteopedia
Crystal Structure of PduOC:Heme Complex
Structural highlights
FunctionPDUO_SALTY Converts cob(I)alamin to adenosylcobalamin (adenosylcob(III)alamin), the cofactor for propanediol dehydratase. Found in the bacterial microcompartment (BMC) dedicated to 1,2-propanediol (1,2-PD) degradation (PubMed:11160088, PubMed:15547259, PubMed:27446048, PubMed:15817784, PubMed:20656910). For adenosylcobalamin synthesis dATP can replace ATP, but no other nucleotides will substitute (PubMed:15547259). PduS and PduO allow regeneration of the adenosylcobalamin cofactor within the BMC (Probable).[1] [2] [3] [4] [5] The 1,2-PD-specific bacterial microcompartment (BMC) concentrates low levels of 1,2-PD catabolic enzymes, concentrates volatile reaction intermediates thus enhancing pathway flux and keeps the level of toxic, mutagenic propionaldehyde low.[6] Publication Abstract from PubMedThe two-domain protein PduO, involved in 1,2-propanediol utilization in the pathogenic Gram-negative bacterium Salmonella enterica is an ATP:Cob(I)alamin adenosyltransferase, but this is a function of the N-terminal domain alone. The role of its C-terminal domain (PduOC) is, however, unknown. In this study, comparative growth assays with a set of Salmonella mutant strains showed that this domain is necessary for effective in vivo catabolism of 1,2-propanediol. It was also shown that isolated, recombinantly-expressed PduOC binds heme in vivo. The structure of PduOC co-crystallized with heme was solved (1.9 A resolution) showing an octameric assembly with four heme moieities. The four heme groups are highly solvent-exposed and the heme iron is hexa-coordinated with bis-His ligation by histidines from different monomers. Static light scattering confirmed the octameric assembly in solution, but a mutation of the heme-coordinating histidine caused dissociation into dimers. Isothermal titration calorimetry using the PduOC apoprotein showed strong heme binding (K d = 1.6 x 10(-7) M). Biochemical experiments showed that the absence of the C-terminal domain in PduO did not affect adenosyltransferase activity in vitro. The evidence suggests that PduOC:heme plays an important role in the set of cobalamin transformations required for effective catabolism of 1,2-propanediol. Salmonella PduO is one of the rare proteins which binds the redox-active metabolites heme and cobalamin, and the heme-binding mode of the C-terminal domain differs from that in other members of this protein family. The Crystal Structure of the C-Terminal Domain of the Salmonella enterica PduO Protein: An Old Fold with a New Heme-Binding Mode.,Ortiz de Orue Lucana D, Hickey N, Hensel M, Klare JP, Geremia S, Tiufiakova T, Torda AE Front Microbiol. 2016 Jun 28;7:1010. doi: 10.3389/fmicb.2016.01010. eCollection, 2016. PMID:27446048[7] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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