• DOI:10.1038/2917
• Corpus ID: 2629199

The early history of lysozyme

@article{Johnson1998TheEH,
  title={The early history of lysozyme},
  author={Louise N. Johnson},
  journal={Nature Structural Biology},
  year={1998},
  volume={5},
  pages={942-944}
}

• L. Johnson
• Published 1 November 1998
• Chemistry, Biology
• Nature Structural Biology

struct used by Rayment at al., and in addition have solved both constructs with ADP.AlF4 bound. In each case they obtain the closed form. Since the crystal forms obtained display a wealth of non-crystallographic symmetry, the closed conformation has now been found 17 times. Little doubt can remain that the closed form represents a biological significant second conformation of the myosin cross bridge. As a bonus, the smooth muscle construct with one light chain (Fig. 2) shows that the light chain has formed a bond with the top of the motor domain (at the expense of the integrity of the lever arm helix, which has been bent by ~8°). Since light chains are involved in the activation and deactivation of smooth muscles, this extra interaction could be part of a control mechanism. The closed form was first found with ADP.AlF4 and ADP.vanadate bound in the active site. Since the geometries of both AlF4 and vanadate are similar to that of the transition state, Smith and Rayment10 suggested that the transition state favors the closed form. However, the equilibrium seems to be delicately poised since both the open and closed forms have now been determined with ADP.BeF3 (refs 1,9, and our unpublished results). Nevertheless, it seems necessary to have the γ-phosphate (or a phosphate analog) in the active site to form the closed form. The myosin power-stroke appears to work by switching between the closed and open conformations. This change is driven by actin binding and phosphate release13. The resulting movement of 0.5 nm in the active site is amplified into a 10 nm movement at the other end of the molecule through a system of molecular gears and levers involving large changes in only a few residues Thus, we now have atomic models of the two important states in the cross bridge cycle which are associated with phosphate release and, in some sense, muscle contraction can be said to be understood at the atomic level. But, naturally, there is much more to learn. How do the two states interconvert during a contraction? How does the binding to actin control the switching between the two states? What happens when there is no nucleotide bound? How does actin-