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Issue 14, 2010
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Importance of loop dynamics in the neocarzinostatin chromophore binding and release mechanisms

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Abstract

Neocarzinostatin (NCS) is an antitumor chromophore carrier protein with many therapeutic applications. To characterize its binding and release mechanism, we have carried out molecular dynamics (MD) simulations for apo-NCS and holo-NCS. Although the β-sheet regions of the protein exhibit restricted motion, large atomic fluctuations were observed in the loop regions, especially loop 99–104. This loop undergoes a “door-opening” motion that can facilitate chromophore binding and release. Calculated NMR order parameters confirm the simulated loop flexibility. We also provide a proposed explanation for the release rate difference for two mutants F78L and F78A through our simulation. The binding site structures of holo-NCS were also validated by chemical shift perturbations. Based on these results, a new binding and release mechanism for the NCS chromophore is proposed.

Graphical abstract: Importance of loop dynamics in the neocarzinostatin chromophore binding and release mechanisms

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Publication details

The article was received on 26 Nov 2009, accepted on 05 Mar 2010 and first published on 10 Mar 2010


Article type: Paper
DOI: 10.1039/B924951F
Citation: Phys. Chem. Chem. Phys., 2010,12, 3443-3449

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    Importance of loop dynamics in the neocarzinostatin chromophore binding and release mechanisms

    B. Wang and K. M. Merz Jr., Phys. Chem. Chem. Phys., 2010, 12, 3443
    DOI: 10.1039/B924951F

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