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Lookup NU author(s): Professor Alastair Hawkins
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Two high-resolution structures have been determined for Eschericia coli aspartate β-semialdehyde dehydrogenase (ecASADH), an enzyme of the aspartate biosynthetic pathway, which is a potential target for novel antimicrobial drugs. Both ASADH structures were of the open form and were refined to 1.95Å and 1.6Å resolution, allowing a more detailed comparison with the closed form of the enzyme than previously possible. A more complex scheme for domain closure is apparent with the subunit being split into two further sub-domains with relative motions about three hinge axes. Analysis of hinge data and torsion-angle difference plots is combined to allow the proposal of a detailed structural mechanism for ecASADH domain closure. Additionally, asymmetric distortions of individual subunits are identified, which form the basis for the previously reported "half-of-the-sites reactivity" (HOSR). A putative explanation of this arrangement is also presented, suggesting the HOSR system may provide a means for ecASADH to offset the energy required to remobilise flexible loops at the end of the reaction cycle, and hence avoid falling into an energy minimum. © 2004 Elsevier Ltd. All rights reserved.
Author(s): Nichols CE, Dhaliwal B, Lockyer M, Hawkins AR, Stammers DK
Publication type: Article
Publication status: Published
Journal: Journal of Molecular Biology
ISSN (print): 0022-2836
ISSN (electronic): 1089-8638
Publisher: Academic Press
PubMed id: 15288787
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