5,10-methenyltetrahydromethanopterin hydrogenase

H2-forming N5,N10-methylene-tetrahydromethanopterin dehydrogenase
the crystal structure of the apoenzyme of the iron-sulfur-cluster-free hydrogenase (hmd)
Identifiers
Symbol	HMD
Pfam	PF03201
InterPro	IPR004889
Available protein structures: Pfam structures PDB RCSB PDB; PDBe; PDBj PDBsum structure summary

The 5,10-methenyltetrahydromethanopterin hydrogenase (or Hmd), the so-called iron-sulfur cluster-free hydrogenase, is an enzyme found in methanogenic archea such as Methanothermobacter marburgensis. It was discovered and first characterized by the Thauer group at the Max Planck Institute in Marburg. Hydrogenases are enzymes that either reduce protons or oxidize molecular dihydrogen.

Methanogens rely on such enzymes to catalyze the reduction of CO₂, to methane. One step in methanogenesis entails conversion of a methenyl group (formic acid oxidation state) to a methylene group (formaldehyde oxidation state).

Among the hydrogenase family of enzymes, Hmd is unique in that it does not directly reduce CO₂ to CH₄. The natural substrate of the enzyme is the organic compound methenyltetrahydromethanopterin. The organic compound includes a methenyl group bound to two tertiary amides. The methenyl group originated as CO₂ before being incorporated into the substrate, which is catalytically reduced by H₂ to methylenetetrahydromethanopterin as shown. Eventually the methylene group is further reduced and released as a molecule of methane.

The hydride transfer has also been shown to be stereospecific. Given that the substrate is planar the hydride originating from H₂ is always added to the pro-R face. In the reverse reaction stereospecificity is maintained and the highlighted hydride is removed.