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mtSNP Database Search

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mtSAP 3D Structure
For further evaluation of the effects of mitochondrial single amino acid polymorphisms (mtSAPs) on the functioning of the mitochondrial respiratory chain, this mtSNP database provides a molecular simulation system that predicts the conformational changes caused by each mtSAP or a group of mtSAPs detected in each individual. At present, the 3-dimensional structures of bovine cytochrome c oxidase and cytochrome bc1 complex (ubiquinol-cytochrome c oxidoreductase) are known. All of the subunits, both mitochondrially encoded and nuclearly encoded, of the bovine enzymes were replaced by those of human enzymes, and then the structures of the human enzymes were calculated by a molecular dynamic simulation system. For each mtSAP or group of mtSAPs that occurred in each individual, the altered structures are predicted by the simulation system in GiiB. These predicted structures will be sent as protein database format (PDB) files by e-mail to each client who has requested them through the 3D Structure section in this mtSNP database. How to use RasMol is here.

example:

15497G>A (Cytb, Gly251S) CytbG251S.pdb
ImposeWt&CytbG251S.pdb

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Prediction of three-dimensional structures of human cytochrome bc1 complex and cytochrome c oxidase
Structure model of human complex III (ubiquinol-cytochrome c oxidoreductase, EC 1.10.2.2, or cytochrome bc1 complex) and human complex IV (cytochrome c oxidase, EC 1.9.3.1) were built by homology modeling. The following procedure was performed with a combination of the Modeler and CHARMm modules from the Insight II program package (Molecular Simulations Inc., San Diego, CA) in a workstation Octane2 (Silicon Graphics Inc., Mountain View, CA). The amino acid sequences of human enzymes were aligned with bovine enzymes. According to the alignment, the models were automatically created on the crystal structures of bovine enzymes (PDB ID: 1QCR reported by Xia et al. and PDB ID: 2OCC by Yoshikawa et al.) by the molecular probability density file (MPDF) method with the Modeler module. Then the structures were refined by simulated annealing on the CHARMm module. To control the procedure automatically, several Perl scripts were constructed. 

1. Xia D, Yu CA, Kim H, Xia JZ, Kachurin AM, Zhang L, Yu L, Deisenhofer J. Crystal structure of the cytochrome bc1 complex from bovine heart mitochondria. Science 277: 60-66; 1997.

2. Yoshikawa S, Shinzawa-Itoh K, Nakashima R, Yaono R, Yamashita E, Inoue N, Yao M, Fei MJ, Libeu CP, Mizushima T, Yamaguchi H, Tomizaki T, Tsukihara T. Redox-coupled crystal structural changes in bovine heart cytochrome c oxidase. Science 280: 1723-1729; 1998.

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