Crystal structure reveals conservation of amyloid-β conformation recognized by 3D6 following humanization to bapineuzumab

Table 3 Summary of mouse VL and VH framework residues retained in humanized 3D6/bapineuzumab based on predicted interactions (<4 Å) with critical distal intra-chain or inter-chain residues

Mouse VL Fr residue retained in bapineuzumab	Interacting residues revealed from crystal structure of 3D6	Mouse VH Fr residue retained in bapineuzumab	Interacting residue revealed from crystal structure of 3D6
V2	Ser26:L1, Gln27:L1	A49	Ser35:H1
V2	His93:L3, Thr97:L3	A49	Ser50:H2, Tyr58:H2 Tyr59:H2
L36	Trp89:L3	V93	Met34:H1, Ser35:H1
L36	Leu45(H), Trp103(H)	V93	Tyr95:H3, Ser100B:H3 Tyr102:H3
R46	Trp35(L), Leu36(L) Asp55:L2, Val58(L)	R94	Tyr32:H1, Met34:H1
	Trp35(L), Leu36(L) Asp55:L2, Val58(L)		Tyr95:H3, Asp96:H3 Ser100B:H3, Asp101:H3 Tyr102:H3
	Ser99:H3, Ser100a:H3 *Ser100b:H3* , Asp101:H3

The residues were retained based on model predictions. The crystal structure of 3D6 confirmed interactions <4 Å between the retained mouse residues and the residues listed above. CDR residues revealed in the structure of 3D6 to directly contact Aβ peptide antigen (from Table 2) are shown as boldface, italicized and boldface font indicates CDR residue that makes an α-carbon backbone contact with the retained mouse residue. CDR residues not contacting antigen are indicated by italics. L1, L2 and L3 indicate light chain CDR1, CDR2, and CDR3 residues respectively, and H1, H2, and H3 indicate heavy chain CDR1, CDR2 and CDR3 residues. Framework (Fr) residues are indicated as unformatted text followed by (H) and (L) to indicate heavy or light chain origin, respectively. CDR, complementarity determining region.

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