Table 2.

Overview of published experimental data supporting 3TM or 4TM topological models for hVKORC1.

Arguments for 3TM hVKORC1 Structure	Arguments for 4TM hVKORC1 Structure
Location of the C-Terminus of VKORC1 in the cytoplasm and of the N-Terminus in the ER-lumen; FFP assay [26]	siRNA knock-down of PDI located in the ER lumen results in reduced VKOR activity [35]
Cys51Ala exhibits VKOR activity = Cys51 is not required for VKOR activity, DTT and cell-based assays [3,26,36]	Cys43Ala/Ser and Cys51Ala/Ser exhibit no VKOR activity = Cys43 and Cys51 are required for VKOR activity, DTT and Trx/TrxR assays [30,33]
hVKOR model, prediction program TOPCONS [37]	Cys43 forms a disulfide bond with four PDIs, immunoprecipitation [27]
	3.6 Å crystal structure of the bacterial homologue of VKOR from Synechococcus sp. in conjunction with multiple sequence alignments [19]
	hVKORC1 model based on crystal structure of synVKOR and putative warfarin binding interfaces that correspond to the reported WR mutations [23]

The left- and right-hand columns present brief summaries of the experimental data obtained from structural studies and assays of VKOR activity (together with literature citations) that support either the 3TM or 4TM topology for hVKORC1 respectively.