Three-dimensional model, homologous

Three-dimensional models can be obtained most easily if the 3D structure of a homologous protein is known (homology modelling, comparative modelling). A homology model can only be as good as the sequence... 

Detailed three-dimensional models of P-gp-substrate complexes representing the various steps of the catalytic cycle would be significantly helpful in elucidating the molecular mechanism for substrate binding and release. The relatively poor 3D structural information available [14—16] and the complex mechanism for compounds undergoing P-gp-compound interactions explain why only a few groups have attempted to build and study 3D homology models for P-gp [56,58,60,70]. 

A rational approach toward the design of class-I isoform selective HDAC inhibitors was reported recently by Wiest et al. [100]. In order to understand the difference between these class-I isoforms, three-dimensional models of HDACl, HDAC2, HDAC3, and HDAC8 were built using homology modeling. 

While the determination of a high-resolution three-dimensional model for Cyt b f remains to be anticipated , the work on the Cyt-6c, complex of mitochondria, by comparison, has been much more advanced than the functionally homologous Cyt-b f Crystals of the Cyt-6c, complex were available... 

Homology modeling of proteins has been of great value in interpreting the relationships of sequence, structure, and function. In particular, orthologous proteins usually show a pattern of conserved residues that can be interpreted in terms of three-dimensional models of the proteins. Conserved... 

M. Jaquinod, N. M. Thielens, J. Gagnon, G. J. Arlaud. Structure and assembly of the catalytic region of human complement protease Clr a three-dimensional model based on chemical cross-linking and homology modeling. Biochemistry. 1997, 36, 6270-6282. 

At present, starting from a protein one-dimensional sequence in order to build a three-dimensional structure is hopeless even for very short sequences. The best way to obtain access to a three-dimensional model is to perform sequence homology building, starting from an X-ray or NMR structure of a similar protein. 

As an example of genome-scale comparative modeling using standard sequence alignment algorithms and MODELLER, Sanchez and Sali [27] recently scanned a portion of the yeast genome, S. cerevisiae [28]. They found homologous proteins of known structure for about 17% of the proteins (1071 sequences), and they built three-dimensional models for these yeast proteins. Only 40 of these modeled proteins had a previously determined experimental structure, and 236 proteins were related to a protein of known structure for the first time. 

MJ Sutcliffe, I Haneef, D Carney, TL Blundell. Knowledge based modelling of homologous proteins. Part I Three dimensional frameworks derived from the simultaneous superposition of multiple structures. Protein Eng 1 377-384, 1987. 

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