Structure of Rhombohedral 2 Zinc Insulin Crystals

Adams, Margaret; Blundell, Tom L.; Dodson, E.J.; Dodson, Guy; Vijayan, M.; Baker, Edward N.; Harding, Marjorie M.; Hodgkin, Dorothy Crowfoot; Rimmer, B.; Sheat, Sylvia V.

doi:10.1038/224491a0

Cited by 502 publications

(297 citation statements)

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“…deviations were calculated for all N, Ca and C backbone a t o m and also for the backbone atoms in the helices separately. The two best DG structures and the averaged structure obtained from the 20-ps RMD run, called the 'NMR structure', were compared with the average RMD structure of des-(B26-B30)-insulin [9] and the pig insulin crystal structures (molecules 1 and 2) [2]. The results of this comparison are reported in Table 3.…”

Section: Striic'ture Determinationmentioning

confidence: 99%

The solution structure of a monomeric insulin

Knegtel

Boelens

Ganadu

et al. 1991

European Journal of Biochemistry

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The solution conformation of des-(B26-B30)-insulin (DPI) has been investigated by 'H-NMR spectroscopy. A set of 250 approximate interproton distance restraints, derived from two-dimensional nuclear Overhauser enhancement spectra, were used as the basis of a structure determination using distance geometry (DG) and distance-bound driven dynamics (DDD). Sixteen DG structures were optimized using energy minimization (EM) and submitted to short 5-ps restrained molecular dynamics (RMD) simulations. A further refinement of the DDD structure with the lowest distance errors was done by energy minimization, a prolonged RMD simulation in VUL'UO and a time-averaged RMD simulation. An average structure was obtained from a trajectory generated during 20-ps RMD. The final structure was compared with the des-(B26 -B30)-insulin crystal structure refined by molecular dynamics and the 2-Zn crystal structure of porcine insulin. This comparison shows that the overall structure of des-(B26 -B30)-insulin is retained in solution with respect to the crystal structures with a high flexibility at the N-terminal part of the A chain and at the N-terminal and C-terminal parts of the B chain. In the RMD run a high mobility of Gly A l , Asn A21 and of the side chain of Phe B25 is noticed. One of the conformations adopted by des-(B26-B30)-insulin in solution is similar to that of molecule 1 (Chinese nomenclature) in the crystal structure of porcine insulin.Due to its biological importance as a hormone and drug, insulin has been the subject of numerous studies regarding its structure and function [l]. Several crystal structures of insulins have been reported [2 -61 and a detailed picture of the spatial structure of insulins has emerged.The insulin molecule consists of two polypeptide chains, A and B, of 21 and 30 residues respectively (cf. Fig. 1). The horse-shoe-shaped A chain contains two helices (residues A2-A8 and A13-A20) and the B chain one helix (residues B9 -BI 9). These chains are connected by two disulphide bridges (A7 -B7 and A20 -B19) which, together with a third one (A6 -A1 I), help stabilize the folded form of insulin over a broad range of temperatures and pH values. In the crystal structures the last six residues of the B chain form an antiparallel fl-sheet with another insulin molecule. Insulin is a rather flexible molecule, as evidenced by large structural differences found in different crystal structures. The major differences between various forms of insulin are in the N-terminal of the B chain. For instance, the porcine 4-Zn insulin structure has an additional helical region running from B1 to B8 [4], whereas in 2-Zn insulin this fragment is in a random coil conformation. In fact, a variety of solution and crystal studies showed that the conversion of the 2-Zn to the 4-Zn structure can be induced by high concentrations of anions [7]. Adding Correspondence to R . Boelens, Department of Chemistry, University of Utrecht, Padualaan 8, 3584 CH Utrecht, The NetherlandsAhbveviutions. Des-(3326 -B30)-insulin, insulin lacking the C-te...

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Section: Striic'ture Determinationmentioning

confidence: 99%

The solution structure of a monomeric insulin

Knegtel

Boelens

Ganadu

et al. 1991

European Journal of Biochemistry

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“…We will present structural basis of specific tRNA recognition in these indirect aminoacyl-tRNA synthesis mechanisms, on the basis of our crystal structures of the machineries in the tRNA-bound form. While the three-dimensional structure of insulin was an early triumph of protein crystallography [1], to date there has been no threedimensional structural information regarding the manner in which the insulin hormone binds to the insulin receptor (IR). Therapeutic targeting of IR is of key importance in the treatment of both Type 1 and Type 2 diabetes and structural information regarding the mode of insulin binding to IR is of particular relevance to the design of novel insulins with enhanced therapeutic profiles [2].…”

Section: Variable-range-hopping Conductivity In Quasicrystalsmentioning

confidence: 99%

“…E-mail: yuri.vekilov@ gmail.com Among icosahedral phases, including single crystals of icosahedral Al-Pd-Re, the variable-range-hopping (VRH) regime is only revealed in polygrain samples of icosahedral Al-Pd-Re with the resistivity ratio R = ρ(4.2 K)/ρ(300 K) ≥ 13. Experiments show that this regime relates to the presence of defects, voids and inclusions of secondary phases [1,2]. Here we analyze the low temperature electronic transport in polygrain samples of icosahedral Al-Pd-Re using an analogy with granular electronic conductors.…”

Section: Variable-range-hopping Conductivity In Quasicrystalsmentioning

confidence: 99%

See 1 more Smart Citation

Structural basis for the sequential assembly of photosynthetic multienzyme complex

Matsumura¹,

Kai²,

Maeda³

et al. 2011

Acta Cryst Sect A

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Microsymposia C145 MSwas used for the modelling process, was calculated using a statistical method [1], which allows a purely 3-dimensional, real space optimization of a quasicrystalline structure. Such an approach has already been successfully used for structure refinement of various modifications of the Al-Ni-Co quasicrystal [2], [3], [4]. This is the very first attempt of quantitative structure optimization of Al-Cu-Ir and Al-Cu-Rh quasicrystals based on high resolution, synchrotron diffraction datasets. Up to now the only structure investigation of an Al-Cu-Rh quasicrystal was based on electron microscopy, the structure of the Al-Cu-Ir quasicrystal has not been studied before and the AlCu-Co structure was refined only based on a rather limited, in-house diffraction dataset. The current refinement gives much more details about the structure.All three decagonal phases show ~4 Å periodicity (two atomic layers per period). Their space group is centrosymmetric P10 5 /mmc. While the Al-Cu-Co phase shows a significant amount of diffuse scattering in the interlayers of the diffraction pattern, the Al-Cu-Ir and Al-Cu-Rh phases exhibit no diffuse scattering. This fact is well-reflected in the structure of Al-Cu-Ir and Al-Cu-Rh phases, i.e. they are wellordered, the Cu/Ir and Cu/Rh positions can clearly be distinguished and the only disorder present is the partial occupation of several Al positions. All decagonal quasicrystals are ternary alloys based on Al and two transition metals. This is the very first structure refinement of a decagonal phase distinguishing the positions of two different transition metal atoms. The initial model for all phases was the same and based on the rhombic Penrose tiling. The initial decoration of the rhombuses was derived based on a structure solution obtained from charge flipping. The refined structure gives reasonable R values, and the chemical composition agrees well with the EDX measurements. The density of electronic states at the Fermi energy N(E F ) in icosahedral quasicrystals is nonzero. We therefore consider a model in which metallic quasicrystalline particles of a size ranging from few nanometers to hundreds of nanometers are embedded into an insulating matrix. The electronic levels are discrete due to electron confinement within a single "grain". The mean level spacing δ is inversely proportional to the volume V of the grain δ =1/[N(E F )V]. For icosahedral Al-Pd-Re δ is an order of magnitude higher that for a typical metal.Two main factors are responsible for the electronic transport in icosahedral Al-Pd-Re. The first is the dimensionless intergranular conductance g. Samples with g ≥ 1 exhibit metallic properties. Samples with g ≤ 1 show an insulating behavior. Depending on the structural state of the material and the temperature, both factors may be important. The notion of granular system means g ≤ g 0 , where g 0 is the dimensionless intragranular conductance. The homogeneously disordered case corresponds to g ≈ g 0 . The second factor is the electrostatic (Coulomb) energ...

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“…In the hexamer, the three dimers are held together by hydrophobic surface contacts and by the coordination around two Zn(II)-ions. 4,5 Insulin is stored as hexamers in the pancreas and is released into the bloodstream where its monomeric form is part of the regulation of the glucose level in the blood. 6 Diabetes, both type 1 and 2, is associated with faults in the regulation of or sensitivity to insulin levels.…”

Section: ■ Introductionmentioning

confidence: 99%