PDBsum entry 5g0r

Transferase

PDB id: 5g0r

Contents

Protein chains

549 a.a.

442 a.a.

248 a.a.

Ligands

F43 ×2

TP7 ×2

Metals

_CL ×3

_MG ×18

_NA ×3

__K

Waters ×2609

PDB id:

5g0r

Name:

Transferase

Title:

Methyl-coenzyme m reductase i from methanothermobacter marburgensis exposed to 3-nitrooxypropanol

Structure:

Methyl-coenzyme m reductase i subunit alpha. Chain: a, d. Synonym: mcr i alpha, coenzyme-b sulfoethylthiotransferase alpha, methyl-coenzyme m reductase. Other_details: in chain a and d residue 257 is a n1-methylhistidine. Residue 271 is a c5-(s)-methylarginine. Residue 400 is a c2-(s)- methylglutamine. Residue 445 is a thioglycine. Residue 450 is a didehydroaspartate. Residue 452 is a s-methylcysteine. Methyl-coenzyme m reductase i subunit beta.

Source:

Methanothermobacter marburgensis. Organism_taxid: 145263. Strain: marburg. Atcc: dsm 2133. Other_details: german collection of microorganisms (dsm). Other_details: german collection of microorganisms (dsm)

Resolution:

1.25Å R-factor: 0.106 R-free: 0.124

Authors:

T.Wagner

Key ref:

E.C.Duin et al. (2016). Mode of action uncovered for the specific reduction of methane emissions from ruminants by the small molecule 3-nitrooxypropanol. Proc Natl Acad Sci U S A, 113, 6172-6177. PubMed id: 27140643 DOI: 10.1073/pnas.1600298113

Date:

22-Mar-16 Release date: 13-Apr-16

Protein chains

P11558  (MCRA_METTM) -  Methyl-coenzyme M reductase I subunit alpha from Methanothermobacter marburgensis (strain ATCC BAA-927 / DSM 2133 / JCM 14651 / NBRC 100331 / OCM 82 / Marburg)

Seq: 550 a.a.

Struc: 549 a.a.*

Protein chains

P11560  (MCRB_METTM) -  Methyl-coenzyme M reductase I subunit beta from Methanothermobacter marburgensis (strain ATCC BAA-927 / DSM 2133 / JCM 14651 / NBRC 100331 / OCM 82 / Marburg)

Seq: 443 a.a.

Struc: 442 a.a.

Protein chains

P11562  (MCRG_METTM) -  Methyl-coenzyme M reductase I subunit gamma from Methanothermobacter marburgensis (strain ATCC BAA-927 / DSM 2133 / JCM 14651 / NBRC 100331 / OCM 82 / Marburg)

Seq: 249 a.a.

Struc: 248 a.a.

* PDB and UniProt seqs differ at 6 residue positions (black crosses)

Enzyme reactions

• Enzyme class: Chains A, B, C, D, E, F: E.C.2.8.4.1 - coenzyme-B sulfoethylthiotransferase.
• Pathway: Methane Biosynthesis
• Reaction: coenzyme B + methyl-coenzyme M = methane + coenzyme M-coenzyme B heterodisulfide

coenzyme B (Bound ligand (Het Group name = TP7) corresponds exactly) + methyl-coenzyme M = methane + coenzyme M-coenzyme B heterodisulfide

• Cofactor: Coenzyme F430

Coenzyme F430 (Bound ligand (Het Group name = F43) matches with 96.83% similarity)

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

reference

DOI no: 10.1073/pnas.1600298113

Proc Natl Acad Sci U S A 113:6172-6177 (2016)

PubMed id: 27140643

Mode of action uncovered for the specific reduction of methane emissions from ruminants by the small molecule 3-nitrooxypropanol.

E.C.Duin, T.Wagner, S.Shima, D.Prakash, B.Cronin, D.R.Yáñez-Ruiz, S.Duval, R.Rümbeli, R.T.Stemmler, R.K.Thauer, M.Kindermann.

ABSTRACT

Ruminants, such as cows, sheep, and goats, predominantly ferment in their rumen plant material to acetate, propionate, butyrate, CO2, and methane. Whereas the short fatty acids are absorbed and metabolized by the animals, the greenhouse gas methane escapes via eructation and breathing of the animals into the atmosphere. Along with the methane, up to 12% of the gross energy content of the feedstock is lost. Therefore, our recent report has raised interest in 3-nitrooxypropanol (3-NOP), which when added to the feed of ruminants in milligram amounts persistently reduces enteric methane emissions from livestock without apparent negative side effects [Hristov AN, et al. (2015) Proc Natl Acad Sci USA 112(34):10663-10668]. We now show with the aid of in silico, in vitro, and in vivo experiments that 3-NOP specifically targets methyl-coenzyme M reductase (MCR). The nickel enzyme, which is only active when its Ni ion is in the +1 oxidation state, catalyzes the methane-forming step in the rumen fermentation. Molecular docking suggested that 3-NOP preferably binds into the active site of MCR in a pose that places its reducible nitrate group in electron transfer distance to Ni(I). With purified MCR, we found that 3-NOP indeed inactivates MCR at micromolar concentrations by oxidation of its active site Ni(I). Concomitantly, the nitrate ester is reduced to nitrite, which also inactivates MCR at micromolar concentrations by oxidation of Ni(I). Using pure cultures, 3-NOP is demonstrated to inhibit growth of methanogenic archaea at concentrations that do not affect the growth of nonmethanogenic bacteria in the rumen.