posted on 2022-12-21, 19:07authored byVladimir Pelmenschikov, Delfim Ferreira, Sofia S. Venceslau, Peter Hildebrandt, Inês A.
C. Pereira, Smilja Todorovic
The noncubane [4Fe-4S] cluster identified in the active
site of
heterodisulfide reductase (HdrB) displays a unique geometry among
Fe–S cofactors found in metalloproteins. Here we employ resonance
Raman (RR) spectroscopy and density functional theory (DFT) calculations
to probe structural, electronic, and vibrational properties of the
noncubane cluster in HdrB from a non-methanogenic Desulfovibrio
vulgaris (Dv) Hildenborough organism. The
immediate protein environment of the two neighboring clusters in DvHdrB is predicted using homology modeling. We demonstrate
that in the absence of substrate, the oxidized [4Fe-4S]3+ cluster adopts a “closed” conformation. Upon substrate
coordination at the “special” iron center, the cluster
core translates to an “open” structure, facilitated
by the “supernumerary” cysteine ligand switch from iron-bridging
to iron-terminal mode. The observed RR fingerprint of the noncubane
cluster, supported by Fe–S vibrational mode analysis, will
advance future studies of enzymes containing this unusual cofactor.