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Title
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Electron density calculations as an extension of protein structure refinement. Streptomyces griseus protease A at 1.5 A resolution.
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Authors
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J.Moult,
F.Sussman,
M.N.James.
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Ref.
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J Mol Biol, 1985,
182,
555-566.
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PubMed id
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Abstract
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Ab initio quantum mechanical calculations have been used to obtain details of
the electron density distribution in a high-resolution refined protein
structure. It is shown that with accurate atomic co-ordinates, electron density
may be calculated with a quality similar to that which can be obtained directly
from crystallographic studies of small organic molecules, and that this density
contains information relevant to the understanding of catalysis. Atomic
co-ordinates from the 1.8 A and 1.5 A resolution refinements of the crystal
structure of protease A from Streptomyces griseus have been used to examine the
influence of the environment on the electron density in the side-chain of the
active site histidine (His57). The neighbouring aspartic acid 102 is the
dominant factor in the environment, and quantum mechanical calculations have
been performed on these two residues. Most interesting from the point of view of
understanding the catalytic process is the effect that Asp102 has on the
electron density in the region of the imidazole nitrogen (N epsilon 2) adjacent
to the active site serine 195. In the positively charged imidazolium species,
there is a polarization of the N epsilon 2-H bond, reducing the bonding density
in a manner that may lower the height of the energy barrier for proton transfer.
In the uncharged imidazole species, the proximity of Asp102 causes a movement of
density from the lone pair region of the N epsilon 2 into the pi bonding region
above and below the plane of the ring. Although it is shown that the primary
effect of the aspartic acid is electrostatic, this movement is perpendicular to
the direction of the electric field inducing it.
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