| Structural highlights
Function
[ACSD_MOOTH] Acts as a methyl group carrier in the anaerobic acetyl-CoA pathway (Wood-Ljungdahl pathway) of carbon monoxide and carbon dioxide fixation.[1] [2] [3] [ACSC_MOOTH] Acts as a methyl group carrier in the anaerobic acetyl-CoA pathway (Wood-Ljungdahl pathway) of carbon monoxide and carbon dioxide fixation.[4] [5] [6]
Publication Abstract from PubMed
Derivatives of vitamin B(12) are used in methyl group transfer in biological processes as diverse as methionine synthesis in humans and CO(2) fixation in acetogenic bacteria. This seemingly straightforward reaction requires large, multimodular enzyme complexes that adopt multiple conformations to alternately activate, protect and perform catalysis on the reactive B(12) cofactor. Crystal structures determined thus far have provided structural information for only fragments of these complexes, inspiring speculation about the overall protein assembly and conformational movements inherent to activity. Here we present X-ray crystal structures of a complete 220 kDa complex that contains all enzymes responsible for B(12)-dependent methyl transfer, namely the corrinoid iron-sulphur protein and its methyltransferase from the model acetogen Moorella thermoacetica. These structures provide the first three-dimensional depiction of all protein modules required for the activation, protection and catalytic steps of B(12)-dependent methyl transfer. In addition, the structures capture B(12) at multiple locations between its 'resting' and catalytic positions, allowing visualization of the dramatic protein rearrangements that enable methyl transfer and identification of the trajectory for B(12) movement within the large enzyme scaffold. The structures are also presented alongside in crystallo spectroscopic data, which confirm enzymatic activity within crystals and demonstrate the largest known conformational movements of proteins in a crystalline state. Taken together, this work provides a model for the molecular juggling that accompanies turnover and helps explain why such an elaborate protein framework is required for such a simple, yet biologically essential reaction.
Visualizing molecular juggling within a B(12)-dependent methyltransferase complex.,Kung Y, Ando N, Doukov TI, Blasiak LC, Bender G, Seravalli J, Ragsdale SW, Drennan CL Nature. 2012 Mar 14. doi: 10.1038/nature10916. PMID:22419154[7]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Kung Y, Ando N, Doukov TI, Blasiak LC, Bender G, Seravalli J, Ragsdale SW, Drennan CL. Visualizing molecular juggling within a B(12)-dependent methyltransferase complex. Nature. 2012 Mar 14. doi: 10.1038/nature10916. PMID:22419154 doi:10.1038/nature10916
- ↑ Roberts DL, James-Hagstrom JE, Garvin DK, Gorst CM, Runquist JA, Baur JR, Haase FC, Ragsdale SW. Cloning and expression of the gene cluster encoding key proteins involved in acetyl-CoA synthesis in Clostridium thermoaceticum: CO dehydrogenase, the corrinoid/Fe-S protein, and methyltransferase. Proc Natl Acad Sci U S A. 1989 Jan;86(1):32-6. PMID:2911576
- ↑ Lu WP, Schiau I, Cunningham JR, Ragsdale SW. Sequence and expression of the gene encoding the corrinoid/iron-sulfur protein from Clostridium thermoaceticum and reconstitution of the recombinant protein to full activity. J Biol Chem. 1993 Mar 15;268(8):5605-14. PMID:8449924
- ↑ Kung Y, Ando N, Doukov TI, Blasiak LC, Bender G, Seravalli J, Ragsdale SW, Drennan CL. Visualizing molecular juggling within a B(12)-dependent methyltransferase complex. Nature. 2012 Mar 14. doi: 10.1038/nature10916. PMID:22419154 doi:10.1038/nature10916
- ↑ Roberts DL, James-Hagstrom JE, Garvin DK, Gorst CM, Runquist JA, Baur JR, Haase FC, Ragsdale SW. Cloning and expression of the gene cluster encoding key proteins involved in acetyl-CoA synthesis in Clostridium thermoaceticum: CO dehydrogenase, the corrinoid/Fe-S protein, and methyltransferase. Proc Natl Acad Sci U S A. 1989 Jan;86(1):32-6. PMID:2911576
- ↑ Lu WP, Schiau I, Cunningham JR, Ragsdale SW. Sequence and expression of the gene encoding the corrinoid/iron-sulfur protein from Clostridium thermoaceticum and reconstitution of the recombinant protein to full activity. J Biol Chem. 1993 Mar 15;268(8):5605-14. PMID:8449924
- ↑ Kung Y, Ando N, Doukov TI, Blasiak LC, Bender G, Seravalli J, Ragsdale SW, Drennan CL. Visualizing molecular juggling within a B(12)-dependent methyltransferase complex. Nature. 2012 Mar 14. doi: 10.1038/nature10916. PMID:22419154 doi:10.1038/nature10916
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