Paper Citing VMD - Abstract
Parthasarathy, Sudharsan, Altuve, Adriana, Terzyan, Simon, Zhang, Xuejun, Kuczera, Krzysztof, Rivera, Mario, Benson, David R.
Accommodating a Nonconservative Internal Mutation by Water-Mediated Hydrogen Bonding between beta-Sheet Strands: A Comparison of Human and Rat Type B (Mitochondrial) Cytochrome b(5)
BIOCHEMISTRY, 50:5544-5554, JUN 21 2011 2011
Mammalian type B (mitochondria b(s) cytochromes exhibit greater amino acid sequence diversity than their type A (microsomal) counterparts, as exemplified by the type B proteins from human (hCYBSB) 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-strand beta-sheet, which can be attributed to fully buried residue 21 in strand beta 4. The greater bulk of Leu21 in hCYB5B in comparison to that of Thr21 in rCYB5B results in a substantial displacement of the first two residues in beta 5, and consequent loss of two of the three hydrogen bonds between beta 5 and beta 4. Hydrogen bonding between the residues is instead mediated by two wellordered, fully buried water molecules. In a 10 ns molecular dynamics simulation, one of the buried water molecules in the hCYBSB structure exchanged readily with solvent via intermediates having three water molecules sandwiched between beta 4 and beta 5. When the buried water molecules were removed prior to a second 10 ns simulation, beta 4 and beta 5 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 access of water to the interior of hCYBSB than of rCYBSB 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 b(s) fold.
