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    Accommodating a Non-Conservative Internal Mutation by WaterMediated Hydrogen-Bonding Between β-Sheet Strands: A Comparison of Human and Rat Type B (Mitochondrial) Cytochrome b5

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    Issue Date
    2011-06-11
    Author
    Parthasarathy, Sudharsan
    Altuve, Adriana
    Terzyan, Simon
    Zhang, Xuejun
    Kuczera, Krzysztof
    Rivera, Mario
    Benson, David R.
    Publisher
    American Chemical Society
    Type
    Article
    Article Version
    Scholarly/refereed, author accepted manuscript
    Rights
    Copyright © 2011 American Chemical Society
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    Abstract
    Mammalian type B (mitochondrial) cytochromes b5 exhibit greater amino acid sequence diversity than their type A (microsomal) counterparts, as exemplified by the type B proteins from human (hCYB5B) and rat (rCYB5B). The comparison of X-ray crystal structures of hCYB5B and rCYB5B reported herein reveals a striking difference in packing involving the five-stranded β-sheet, attributable to fully buried residue 21 in strand β4. The greater bulk of Leu21 in hCYB5B in comparison to Thr21 in rCYB5B results in a substantial displacement of the first two residues in β5, and consequent loss of two of the three hydrogen bonds between β5 and β4. Hydrogen-bonding between the residues is instead mediated by two well-ordered, fully buried water molecules. In a 10 ns molecular dynamics simulation, one of the buried water molecules in the hCYB5B structure exchanged readily with solvent via intermediates having three water molecules sandwiched between β4 and β5. When the buried water molecules were removed prior to a second 10 ns simulation, β4 and β5 formed persistent hydrogen bonds identical to those in rCYB5B, but the Leu21 side chain was forced to adopt a rarely observed conformation. Despite the apparently greater ease of water access to the interior of hCYB5B than of rCYB5B suggested by these observations, the two proteins exhibit virtually identical stability, dynamic and redox properties. The results provide new insight into the factors stabilizing the cytochrome b5 fold.
    URI
    http://hdl.handle.net/1808/23646
    DOI
    https://doi.org/10.1021/bi2004729
    Collections
    • Molecular Biosciences Scholarly Works [581]
    Citation
    Parthasarathy, S., Altuve, A., Terzyan, S., Zhang, X., Kuczera, K., Rivera, M., & Benson, D. R. (2011). Accommodating a Non-Conservative Internal Mutation by Water-Mediated Hydrogen-Bonding Between β-Sheet Strands: A Comparison of Human and Rat Type B (Mitochondrial) Cytochrome b5. Biochemistry, 50(24), 5544–5554. http://doi.org/10.1021/bi2004729

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    Contact KU ScholarWorks
    785-864-8983
    KU Libraries
    1425 Jayhawk Blvd
    Lawrence, KS 66045
    785-864-8983

    KU Libraries
    1425 Jayhawk Blvd
    Lawrence, KS 66045
    Image Credits
     

     

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