title: PQQ-dependent methanol dehydrogenases: rare-earth elements make a difference.
abstract: Methanol dehydrogenase (MDH) catalyzes the first step in methanol use by methylotrophic bacteria and the second step in methane conversion by methanotrophs. Gram-negative bacteria possess an MDH with pyrroloquinoline quinone (PQQ) as its catalytic center. This MDH belongs to the broad class of eight-bladed β propeller quinoproteins, which comprise a range of other alcohol and aldehyde dehydrogenases. A well-investigated MDH is the heterotetrameric MxaFI-MDH, which is composed of two large catalytic subunits (MxaF) and two small subunits (MxaI). MxaFI-MDHs bind calcium as a cofactor that assists PQQ in catalysis. Genomic analyses indicated the existence of another MDH distantly related to the MxaFI-MDHs. Recently, several of these so-called XoxF-MDHs have been isolated. XoxF-MDHs described thus far are homodimeric proteins lacking the small subunit and possess a rare-earth element (REE) instead of calcium. The presence of such REE may confer XoxF-MDHs a superior catalytic efficiency. Moreover, XoxF-MDHs are able to oxidize methanol to formate, rather than to formaldehyde as MxaFI-MDHs do. While structures of MxaFI- and XoxF-MDH are conserved, also regarding the binding of PQQ, the accommodation of a REE requires the presence of a specific aspartate residue near the catalytic site. XoxF-MDHs containing such REE-binding motif are abundantly present in genomes of methylotrophic and methanotrophic microorganisms and also in organisms that hitherto are not known for such lifestyle. Moreover, sequence analyses suggest that XoxF-MDHs represent only a small part of putative REE-containing quinoproteins, together covering an unexploited potential of metabolic functions.
authors.affiliation: Department of Microbiology, Institute of Wetland and Water Research, Radboud University Nijmegen, Heyendaalseweg 135, 6525AJ, Nijmegen, The Netherlands.
authors.forename: Jan T
authors.initials: JT
authors.lastname: Keltjens
authors.forename: Arjan
authors.initials: A
authors.lastname: Pol
authors.forename: Joachim
authors.initials: J
authors.lastname: Reimann
authors.forename: Huub J M
authors.initials: HJ
authors.lastname: Op den Camp
mesh_terms: D000429:Alcohol Oxidoreductases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D003067:Coenzymes / Q000378:metabolism*; D006090:Gram-Negative Bacteria / Q000201:enzymology* / Q000235:genetics; D008697:Methane / Q000378:metabolism; D000432:Methanol / Q000378:metabolism; D008958:Models, Molecular; D045542:PQQ Cofactor / Q000378:metabolism*; D010802:Phylogeny; D011487:Protein Conformation; D021122:Protein Subunits / Q000378:metabolism
chemical_list: D003067:Coenzymes; D021122:Protein Subunits; D045542:PQQ Cofactor; D000429:Alcohol Oxidoreductases; C019641:alcohol dehydrogenase (acceptor); D008697:Methane; D002118:Calcium; D000432:Methanol