Structure-based alignment

Fig. 5. Structure-based alignment of the sequences of the water-soluble Rieske fragment from bovine heart bci complex (ISF), the water-soluble Rieske fragment from spinach b f complex (RFS), and of the Rieske domain of naphthalene dioxygenase (NDO) and of the metal binding loops of rubredoxin (RXN) and transcriptional factor TFIIS (TFI). The numbering of the j3 strands is the same for the ISF and RFS. The metal binding ligands are highlighted the asterisks indicate those residues that are fully conserved between the three Rieske proteins.

Fig. 1.1. The phylogenetic structure of the Nematoda revealed by small subunit ribosomal RNA analysis. (A) Neighbour-joining (NJ) analysis of aligned ssu rRNA genes from nematodes. The alignment is based on that of Blaxter etal. (1998), with the addition of sequences from Aleshin etal. (1998), Nadler (1998)...

Johnson and Overington (1993) measured alignment accuracy and found good performance for structure-based, BLOSUM, and Gonnet matrices. As in other studies, log-odds matrices performed the best. 

Multiple alignments of repeats are constructed in an iterative manner. The initial alignment is based on definitions from determined protein structures or else from the literature. In the initial database search step, a profile constructed from the multiple alignment is compared with a sequence database. Top scoring sequences are considered using complementary approaches such as PSI-BLAST and FASTA to provide the two thresholds minimum E value and minimum number of repeats per protein required. After one or two iterations, the final alignment and the thresholds are stored in the SMART database to allow the detection of repeats in any sequence. 

Structural alignments (ligand-based virtual screening) on the basis of a known active compound, molecules that show a good superimposition in shape and physicochemical features are searched for. 

Cho, S. J. Garsia, M. L. Bier, J. Tropsha, A. Structure-based alignment and comparative molecular field analysis of acetylcholinesterase inhibitors. J. Med. Chem. 1996, 39, 5064-5071. 

With the structure of ascorbate oxidase in hand, a new structurally based alignment of the sequences of ascorbate oxidase, laccase, and ceruloplasmin has been performed (Messerschmidt and Huber, 1990). In brief, while gene triplication for ceruloplasmin is still revelant, its sequence can be further subdivided into two domains per unit of triplicated sequence, or six domains in total. Each of these sequences bears some resemblance to each of the three domains of ascorbate oxidase, as does each of the two domains in laccase. The coppers of the trinuclear site of ceruloplasmin then are predicted to be bound between domains 1 and 6, with a type I site also lying in both domains 6 and 4 (see Huber, 1990). The relative orientation of each of these domains is not predicted by this alignment, but it turns out that the structure of nitrite reductase may shed some light on this (see Section V,C). 

Application of Structure-based Alignment Methods for 3D QSAR Analyses... 

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