Figure 1 Superposition of the bis histidyl orange and ligand bound blue

Figure 1 superposition of the bis histidyl orange and

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Figure 1.Superposition of the bis-histidyl (orange) and ligand-bound (blue)hexacoordinated structures of (a) AHb1 and (b) AHb2.The two proteins exhibit a large resemblance in the overall profiles obtained for thethermal fluctuations of residues (Figure 2). For the bis-histidyl hexacoordinatedproteins the most relevant fluctuations (excluding the N- and C-terminal segments)are related to loops CD (residues 49-65) and EF (residue 87-95). Compared to the bis-histidyl hexacoordinated state, binding of O2to the heme reduces the thermalfluctuations of loop CD (Figure 2). The RMSF profiles obtained for oxygenatedAHb1 and AHb2 are very similar, though helices A and G exhibit somewhat largerfluctuations in AHb1.Overall, the results point out that there is a large similarity between the averagestructural features of the two globins in both bis-histidyl and ligand-bound
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hexaccordinated states, as well as in the structural changes triggered upon binding ofthe exogenous ligand.Figure 2.RMSF (Å) of residues for the (top) bis-histidyl and (bottom) ligand-boundhexacoordinated forms of AHb1 (red) and AHb2 (black).3.2. Essential dynamics.ED analysis was used to investigate the principal motions of the protein backbonefor AHb1 and AHb2 in their different coordination states. The contribution of the firstprincipal components to the structural variance is given in Table 2. In all cases thefirst five essential motions account for around 50% of the structural variance of theprotein backbone. For the bis-histidyl hexacoordinated proteins the first eigenvector
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alone accounts for about 21% of the backbone dynamics along the trajectory. Itscontribution increases up to 34% in O2AHb1, but remains at the same percentage forO2AHb2 (20%). This suggests that ligand binding involves distinct changes in theoverall motions in the protein backbone of AHb1 and AHb2. Table 2. Contribution (%) of the first 10 eigenvectors derived from essentialdynamics to the conformational flexibility of the protein backbone.Essential modehAHb1hAHb2O2AHb1 O2AHb2 120.722.034.520.2214.613.66.99.636.68.55.87.944.45.84.35.554.14.63.73.8cumulative50.454.555.247.0Figure 3 shows the first and final frames of the backbone deformation based on thefirst eigenvector for each protein. For hAHb1 (Figure 3a), the flexibility of the proteinbackbone affects the CD and EF loops, which is accompanied by the swinging of thelast part of helix E and tilting of helix F, while the rest of the backbone shows norelevant displacements. Compared to hAHb1, two major differences are found forhAHb2. First, the backbone rearrangement in the EF region is primarily confined tothe loop, so that the helix F does not show a significant structural rearrangement.Second, the largest deformations of the protein backbone in hAHb2 involve the CDloop and the concomitant displacement of helices B and C. Minor contributions due tothe AB and FG loops and the terminal and initial segments of helices F and G,respectively (Figure 3b) are also observed.
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  • Spring '14
  • ALANNASCHEPARTZ
  • Hemoglobin

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