4DJD

Crystal structure of folate-free corrinoid iron-sulfur protein (CFeSP) in complex with its methyltransferase (MeTr)

Summary for 4DJD

• Entry DOI: 10.2210/pdb4djd/pdb
• Related: 4DJE 4DJF
• Descriptor: 5-methyltetrahydrofolate corrinoid/iron sulfur protein methyltransferase, Corrinoid/iron-sulfur protein large subunit, Corrinoid/iron-sulfur protein small subunit, ... (8 entities in total)
• Functional Keywords: tim barrel, rossmann fold, b12-dependent methyltransferase, transferase-vitamin-binding protein complex, transferase/vitamin-binding protein
• Biological source: Moorella thermoacetica; More
• Total number of polymer chains: 6
• Total formula weight: 228269.65

Authors

Kung, Y.,Doukov, T.I.,Blasiak, L.C.,Drennan, C.L. (deposition date: 2012-02-01, release date: 2012-03-14, Last modification date: 2024-02-28)

Primary citation

Kung, Y.,Ando, N.,Doukov, T.I.,Blasiak, L.C.,Bender, G.,Seravalli, J.,Ragsdale, S.W.,Drennan, C.L.
Visualizing molecular juggling within a B12-dependent methyltransferase complex.
Nature, 484:265-269, 2012

PubMed Abstract: 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.

PubMed: 22419154
DOI: 10.1038/nature10916

Experimental method

X-RAY DIFFRACTION (2.38 Å)