In this study, we show by computer modelling that activated BSS containing a radical on Gly829 (1) requires bound substrates or product to enable H-transfer or H/D exchange between Cys493 and the glycyl radical while these reactions are precluded in apo-BSS; retains the H-or D-atoms of the glycyl radicals when acting with the preferred stereospecificity, but (3) is able to initiate H/D exchange into the glycyl radical at a slow rate (as well as even slower reverse D/H exchange) by occasional reactivity in the non-preferential stereospecifity, together with (4) some experimental support for these predictions. The behavior of the enzyme reported here may be valid for all GRE, indicating that substrate or product binding may be a prerequisite for both H-transfer between the active site Gly and Cys residues and the reactions involved in H/D exchange of the glycyl radical. Since BSS has so far been only investigated in the naturally activated state in cell extracts while in-vitro activation is difficult and has only recently been accomplished , a broader data basis with biochemically better accessible GRE will be very helpful to further investigate the alleged requirements proposed in this study.