| Structural highlights
2ogy is a 2 chain structure with sequence from Atcc 35608. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Ligands: | , |
| Related: | 1f6y, 1q8j, 1aj0, 1ad4, 1tx0, 1tww |
| Gene: | acsE (ATCC 35608) |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum |
Function
[ACSE_MOOTH] Methyltransferase that mediates the transfer of a N5-methyl group of (6S)-methyltetrahydrofolate to the 5-methoxybenzimidazolylcobamide cofactor of a corrinoid/Fe-S protein in the anaerobic acetyl-CoA pathway (Wood-Ljungdahl pathway) of carbon monoxide and carbon dioxide fixation.[1] [2] [3]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
The methyltetrahydrofolate (CH(3)-H(4)folate) corrinoid-iron-sulfur protein (CFeSP) methyltransferase (MeTr) catalyzes transfer of the methyl group of CH(3)-H(4)folate to cob(I)amide. This key step in anaerobic CO and CO(2) fixation is similar to the first half-reaction in the mechanisms of other cobalamin-dependent methyltransferases. Methyl transfer requires electrophilic activation of the methyl group of CH(3)-H(4)folate, which includes proton transfer to the N5 group of the pterin ring and poises the methyl group for reaction with the Co(I) nucleophile. The structure of the binary CH(3)-H(4)folate/MeTr complex (revealed here) lacks any obvious proton donor near the N5 group. Instead, an Asn residue and water molecules are found within H-bonding distance of N5. Structural and kinetic experiments described here are consistent with the involvement of an extended H-bonding network in proton transfer to N5 of the folate that includes an Asn (Asn-199 in MeTr), a conserved Asp (Asp-160), and a water molecule. This situation is reminiscent of purine nucleoside phosphorylase, which involves protonation of the purine N7 in the transition state and is accomplished by an extended H-bond network that includes water molecules, a Glu residue, and an Asn residue (Kicska, G. A., Tyler, P. C., Evans, G. B., Furneaux, R. H., Shi, W., Fedorov, A., Lewandowicz, A., Cahill, S. M., Almo, S. C., and Schramm, V. L. (2002) Biochemistry 41, 14489-14498). In MeTr, the Asn residue swings from a distant position to within H-bonding distance of the N5 atom upon CH(3)-H(4)folate binding. An N199A variant exhibits only approximately 20-fold weakened affinity for CH(3)-H(4)folate but a much more marked 20,000-40,000-fold effect on catalysis, suggesting that Asn-199 plays an important role in stabilizing a transition state or high energy intermediate for methyl transfer.
Structural and kinetic evidence for an extended hydrogen-bonding network in catalysis of methyl group transfer. Role of an active site asparagine residue in activation of methyl transfer by methyltransferases.,Doukov TI, Hemmi H, Drennan CL, Ragsdale SW J Biol Chem. 2007 Mar 2;282(9):6609-18. Epub 2006 Dec 15. PMID:17172470[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Doukov TI, Hemmi H, Drennan CL, Ragsdale SW. Structural and kinetic evidence for an extended hydrogen-bonding network in catalysis of methyl group transfer. Role of an active site asparagine residue in activation of methyl transfer by methyltransferases. J Biol Chem. 2007 Mar 2;282(9):6609-18. Epub 2006 Dec 15. PMID:17172470 doi:http://dx.doi.org/10.1074/jbc.M609828200
- ↑ 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, Zhao S, Doukov T, Ragsdale SW. The reductive acetyl coenzyme A pathway: sequence and heterologous expression of active methyltetrahydrofolate:corrinoid/iron-sulfur protein methyltransferase from Clostridium thermoaceticum. J Bacteriol. 1994 Oct;176(19):6127-30. PMID:7928975
- ↑ Doukov TI, Hemmi H, Drennan CL, Ragsdale SW. Structural and kinetic evidence for an extended hydrogen-bonding network in catalysis of methyl group transfer. Role of an active site asparagine residue in activation of methyl transfer by methyltransferases. J Biol Chem. 2007 Mar 2;282(9):6609-18. Epub 2006 Dec 15. PMID:17172470 doi:http://dx.doi.org/10.1074/jbc.M609828200
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