The structure of desheptapeptide (B24-B30) insulin (DHPI) in a new crystal form (form B) has been determined and refined to 0.2 nm resolution. The crystals were obtained under the same crystallization condition as pre...The structure of desheptapeptide (B24-B30) insulin (DHPI) in a new crystal form (form B) has been determined and refined to 0.2 nm resolution. The crystals were obtained under the same crystallization condition as previously reported crystal form (form A) . The overall structures of the two crystal forms are similar but obvious differences can be observed in crystal packing and local conformation. The crystal structures of the two forms show that the two independent molecules in an asymmetric unit from a DHPI dimer, and the dimer formation buries more than 18.20 and 16.95 nm2 of solvent accessible surfaces for form A and form B DHPI, respectively, the largest among insulin and insulin analogs ever reported. Close examination at crystal packing shows that the dimer-forming surface of DHPI, namely Surface Ⅱ, is normally present in the association of insulin and insulin analogs in their crystal structures. The results demonstrate that Surface II is crucially important for the formation of two crystal forms under the same crystallization condition .展开更多
Desheptapeptide (B24 B30) insulin (DHPI), a virtually inactive insulin analog, has been crystallized in space group P2\-12\-12\-1 with two DHPI molecules in an asymmetric unit. The orientations and positions of the mo...Desheptapeptide (B24 B30) insulin (DHPI), a virtually inactive insulin analog, has been crystallized in space group P2\-12\-12\-1 with two DHPI molecules in an asymmetric unit. The orientations and positions of the molecules were determined by molecular replacement, and a structural model was built at 0.3 nm resolution. The current model shows that the two DHPI monomers are related by a non crystallographic 2 fold axis, nearly parallel to the crystallographic c axis. This structural feature complicated the determination of the orientation of the local 2 fold axis, which was later confirmed by analysing the diffraction data of DHPI crystals.展开更多
Desheptapeptide (B24—B30)-insulin (DHPI), an essentially inactive insulin analog, is crystallized in space group P2_12_12_1 with two molecules in an asymmetric unit. The orientations of the molecules in the crystal c...Desheptapeptide (B24—B30)-insulin (DHPI), an essentially inactive insulin analog, is crystallized in space group P2_12_12_1 with two molecules in an asymmetric unit. The orientations of the molecules in the crystal cell have been determined by using Patterson search method at 6 resolution and the positions of the molecules are deduced from translation function calculation and R search at 3. resolution. After using the rigid body refinement (CORELS) further to refine the orientational and positional parameters as well as the initial energy restrained refinement (EREF) for the model, the crystallographic R valueis reduced to 0.384 at 3 resolution. The initial Fourier map shows that the B-chain N-terminal (B1—B8) and C-terminal (B20—B22)segments, compared with the native 2 zinc insulin, exhibit drastic conformational changes, but the three helices of B- and A-chains and their relative arrangement are essentially kept in DHPI.展开更多
基金Project supported by the National Natural Science Foundation of China (Grant No. 39270156)the Chinese Academy of Sciences
文摘The structure of desheptapeptide (B24-B30) insulin (DHPI) in a new crystal form (form B) has been determined and refined to 0.2 nm resolution. The crystals were obtained under the same crystallization condition as previously reported crystal form (form A) . The overall structures of the two crystal forms are similar but obvious differences can be observed in crystal packing and local conformation. The crystal structures of the two forms show that the two independent molecules in an asymmetric unit from a DHPI dimer, and the dimer formation buries more than 18.20 and 16.95 nm2 of solvent accessible surfaces for form A and form B DHPI, respectively, the largest among insulin and insulin analogs ever reported. Close examination at crystal packing shows that the dimer-forming surface of DHPI, namely Surface Ⅱ, is normally present in the association of insulin and insulin analogs in their crystal structures. The results demonstrate that Surface II is crucially important for the formation of two crystal forms under the same crystallization condition .
文摘Desheptapeptide (B24 B30) insulin (DHPI), a virtually inactive insulin analog, has been crystallized in space group P2\-12\-12\-1 with two DHPI molecules in an asymmetric unit. The orientations and positions of the molecules were determined by molecular replacement, and a structural model was built at 0.3 nm resolution. The current model shows that the two DHPI monomers are related by a non crystallographic 2 fold axis, nearly parallel to the crystallographic c axis. This structural feature complicated the determination of the orientation of the local 2 fold axis, which was later confirmed by analysing the diffraction data of DHPI crystals.
基金Project supported by the National Natural Science Foundation of China
文摘Desheptapeptide (B24—B30)-insulin (DHPI), an essentially inactive insulin analog, is crystallized in space group P2_12_12_1 with two molecules in an asymmetric unit. The orientations of the molecules in the crystal cell have been determined by using Patterson search method at 6 resolution and the positions of the molecules are deduced from translation function calculation and R search at 3. resolution. After using the rigid body refinement (CORELS) further to refine the orientational and positional parameters as well as the initial energy restrained refinement (EREF) for the model, the crystallographic R valueis reduced to 0.384 at 3 resolution. The initial Fourier map shows that the B-chain N-terminal (B1—B8) and C-terminal (B20—B22)segments, compared with the native 2 zinc insulin, exhibit drastic conformational changes, but the three helices of B- and A-chains and their relative arrangement are essentially kept in DHPI.
