2YCK: Methyltransferase Bound With Tetrahydrofolate

Citation:
Abstract
Several anaerobic acetogenic, methanogenic, hydrogenogenic, and sulfate-reducing microorganisms are able to use the reductive acetyl-CoA (Wood-Ljungdahl) pathway to convert CO(2) into biomass. The reductive acetyl-CoA pathway consists of two branches connected by the Co/Fe-containing corrinoid iron-sulfur protein (CoFeSP), which transfers a methyl group from a methyltransferase (MeTr)/methyltetrahydrofolate (CH(3)-H(4) folate) complex to the reduced Ni-Ni-[4Fe-4S] cluster (cluster A) of acetyl-CoA synthase. We investigated the CoFeSP and MeTr couple of the hydrogenogenic bacterium Carboxydothermus hydrogenoformans and show that the two proteins are able to catalyze the methyl-group transfer reaction from CH(3)-H(4) folate to the Co(I) center of CoFeSP. We determined the crystal structures of both proteins. The structure of CoFeSP includes the previously unresolved N-terminal domain of the large subunit of CoFeSP, revealing a unique four-helix-bundle-like architecture in which a [4Fe-4S] cluster is shielded by hydrophobic amino acids. It further reveals that the corrinoid and the [4Fe-4S] cluster binding domains are mobile, which is mandatory for the postulated electron transfer between them. Furthermore, we solved the crystal structures of apo-MeTr, CH(3)-H(4)-folate-bound MeTr, and H(4)-folate-bound MeTr, revealing a substrate-induced closure of the CH(3)-H(4) folate binding cavity of MeTr. We observed three different conformations of Asn200 depending on the substrate bound in the active site, demonstrating its conformational modulation by hydrogen-bonding interactions with the substrate. The observed flexibility could be essential to stabilize the transition state during methyl-group transfer. The conformational space and role of Asn200 are likely conserved in homologous cobalamin-dependent MeTrs such as methionine synthase.
PDB ID: 2YCKDownload
MMDB ID: 91151
PDB Deposition Date: 2011/3/16
Updated in MMDB: 2011/08
Experimental Method:
x-ray diffraction
Resolution: 2.15  Å
Source Organism:
Similar Structures:
Biological Unit for 2YCK: dimeric; determined by author and by software (PISA)
Molecular Components in 2YCK
Label Count Molecule
Proteins (2 molecules)
2
5-methyltetrahydrofolate Corrinoid/iron Sulfur Protein Methyltransferase
Molecule annotation
Chemicals (18 molecules)
1
14
2
2
3
2
* Click molecule labels to explore molecular sequence information.

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