A silent H-bond can be mutationally activated for high-affinity interaction of BMP-2 and activin type IIB receptor

Table 2 Type II receptor specificity of wildtype BMP-2 and variants (Biosensor analysis)

	Receptor ectodomain proteins
BMP-2 (immobilized)	ActR-IIB	ActR-II	BMPR-II
	rel. K_D (app. K_D in nM)
wildtype^a	1 (2700)	1 (5500)	1 (24000)
S85R	1.3	0.85	0.12
A86P	2.6	1.5	0.50
S85R/A86P	1.4	1.3	0.19
L100K	0.15	0.84	1.3
N102D	7.8	3.6	0.96
L100K/N102D	0.05	0.29	0.92
Act-A^b	0.02 (60)	0.04 (230)	0.36 (8700)
BMP-7^b	1 (2800)	0.09 (430)	1.3 (32000)

a) BMP-2 variants were expressed in E. coli. Note, that the wildtype BMP-2 expressed in E. coli has a higher affinity to ActR-IIB than the glycosylated BMP-2 produced in CHO cells (see Table 1)
b) the relative binding constant (normalized to E. coli BMP-2 as a reference) of BMP-7 and Act-A are given for comparison.

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