Sequence and structure alignment

Holm L and C Sander 1999. Protein Folds and Families Sequence and Structure Alignments. Ni Acids Research 27 244-247. 

L Holm, C Sander. Protein folds and families Sequence and structure alignments. Nucleic Acids Res 27 244-247, 1999. 

Figure 6. An example of inter-family target hopping between human and viral aspartyl proteases. The aspartyl protease active site is located at a homodimer interface in HIV and within a single domain in Cathepsin D, so sequence and structure alignments between these proteins cannot be constructed. By using an approach independent of sequence or structure homology to directly align the sites, SiteSorter finds that the HIV protease and Cathepsin D substrate sites are highly similar (identical chemical groups within 1 A are colored dark blue). It has been verified experimentally that Cathepsin D is susceptible to inhibition by HIV-protease inhibitors. ...

In proteins with a symmetric structure, circular permutation can account for the shift of active-site residues over the course of evolution. A very good model of symmetric proteins are the (/Ja)8-barrel enzymes with their typical eightfold symmetry. Circular permutation is characterized by fusion of the N and C termini in a protein ancestor followed by cleavage of the backbone at an equivalent locus around the circular structure. Both fructose-bisphosphate aldolase class I and transaldolase belong to the aldolase superfamily of (a/J)8-symmetric barrel proteins both feature a catalytic lysine residue required to form the Schiff base intermediate with the substrate in the first step of the reaction (Chapter 9, Section 9.6.2). In most family members, the catalytic lysine residue is located on strand 6 of the barrel, but in transaldolase it is not only located on strand 4 but optimal sequence and structure alignment with aldolase class I necessitates rotation of the structure and thus circular permutation of the jS-barrel strands (Jia, 1996). 

A trend in CYP homology model building is clearly toward an integrated approach of multiple sequence and structural alignments, combination with new or available pharmacophore models, automated docking, MD simulations and validation with mutational, spectroscopic, structural, and enzyme kinetic data. Predictions of substrate selectivities and sites of metabolism have been successful for homology models of several CYP isoforms, and, for example, recent... 

There is another type of hot spot determination methods structure-based qualitative methods. The PP SITE method uses hydrogen bonds and hydrophobic characteristics to describe interactions between proteins and to decompose the contribution of atoms in hot spot residues.4 Hu et al derived another qualitative method recently based in the sequence and structure alignments proteins. Residues are characterized as hot spots based in their conserved, polar characteristics.98... 

Holm, L., and Sander, C., 1999, Protein folds and families sequence and structure alignments. 

Residue numbering for human lactoferrin. Deduced from sequence and structure alignment. 

Sequence and structure alignment. Malard et al. (2004) formulate the de novo peptide identification as a constrained MOOP. The objectives considered in the study were the maximization of the similarity between portions of two peptides, and the maximization of the likelihood ratio between the null hypothesis and the alternative hypothesis. 

Thiele, R., R. Zimmer, and T. Fengauer, Recursive dynamic programming for adaptive sequence and structure alignment. Proc Int Conflntell Syst Mol Biol, 1995. 3 p. 384-92. 

Panchenko, A. R. and Bryant, S. H. (2002) A comparison of position-specific score matrices based on sequence and structure alignments. Protein Sci. 11, 361-370. 

Colman PM, Hoyne PA, Lawrence MC (1993) Sequence and structure alignment of paramyxovirus hemagglutinin-neuraminidase with influenza virus neuraminidase. J Virol 67 2972-2980... 

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