Homologous structures

Figure 9 Relative accuracy of comparative models. Upper left panel, comparison of homologous structures that share 40% sequence identity. Upper right panel, conformations of ileal lipid-binding protein that satisfy the NMR restraints set equally well. Lower left panel, comparison of two independently determined X-ray structures of interleukin 1(3. Lower right panel, comparison of the X-ray and NMR structures of erabutoxin. The figure was prepared using the program MOLSCRIPT [236].

SY Chung, S Subbiah. A structural explanation for the twilight zone of protein sequence homology. Structure 4 1123-1127, 1996. 

If the sequence of a protein has more than 90% identity to a protein with known experimental 3D-stmcture, then it is an optimal case to build a homologous structural model based on that structural template. The margins of error for the model and for the experimental method are in similar ranges. The different amino acids have to be mutated virtually. The conformations of the new side chains can be derived either from residues of structurally characterized amino acids in a similar spatial environment or from side chain rotamer libraries for each amino acid type which are stored for different structural environments like beta-strands or alpha-helices. 

Natural mutation of amino acids in the core of a protein can stabilize the same fold with different complementary amino acid types, but they can also cause a different fold of that particular portion. If the sequence identity is lower than 30% it is much more difficult to identify a homologous structure. Other strategies like secondary structure predictions combined with knowledge-based rules about reciprocal exchange of residues are necessary. If there is a reliable assumption for common fold then it is possible to identify intra- and intermolecular interacting residues by search for correlated complementary mutations of residues by correlated mutation analysis, CMA (see e.g., http //www.fmp-berlin.de/SSFA). 

Figure 2. Comparison of the various structure types belonging to two homologous structure series based on the CeCojBj, CaCuj and MgZn2 structure types.

This mutagenesis is very tricky to carry out in a predictable way, unless you have additional structural information that may aid you in this (for instance a homologous structure). 

Other LAS homolog structural effects on wettability and soil removal were found when the data were analyzed using the cohesive energy ratio, R, the regular solution theories of the... 

The receptors for acetylcholine, GABA, glycine and serotonin have a homologous structure and form a superfamily. The best-investigated representative of this superfamUy is the nicotinic acetylcholine receptor, for which extensive biochemical and structural data are available. The nicotinic acetylcholine receptor can be treated as a representative of the other receptors of the superfamUy since it can be assumed that the structure-function principles of this receptor apply to the others. 

Crystals of pronase-released heads of the N2 human strains of A/Tokyo/3/67 [44] and A/RI/5+/57 were used for an x-ray structure determination. The x-ray 3-dimensional molecular structure of neuraminidase heads was determined [45] for these two N2 subtypes by a novel technique of molecular electron density averaging from two different crystal systems, using a combination of multiple isomorphous replacement and noncrystallographic symmetry averaging. The structure of A/Tokyo/3/67 N2 has been refined [46] to 2.2 A as has the structures of two avian N9 subtypes [47-49]. Three influenza type structures [50] have also been determined and found to have an identical fold with 60 residues (including 16 conserved cysteine residues) being invariant. Bacterial sialidases from salmonella [51] and cholera [52] have homologous structures to influenza neuraminidase, but few of the residues are structurally invariant. 

Because peptidoglycans are unique to bacterial cell walls, with no known homologous structures in mammals, the enzymes responsible for their synthesis are ideal targets for antibiotic action. Antibiotics that hit specific bacterial targets are sometimes called magic bullets. Penicillin and its many synthetic analogs have been used to treat bacterial infections since these drugs came into wide application in World War II. 

Comparing homologous structures by least-squares superposition of one protein backbone on another. The result is a new coordinate set for one... 

Although sequence homology modeling of QH-ADHj has been carried out, the problem is that this is not possible for the heme c-containing C-terminal part because a homologous structure and sequence are not available for it. However, on the basis of calculations for the most efficient pathway for electron transfer between PQQH2 and the heme c group, a structure has been proposed for QH-ADH from Comamonas testosteroni [55a] that explains several mechanistic features of this enzyme [69],... 

Unique hair types No homologous structure Vibrissae... 

An understanding of the determinants of substrate specificity has been significantly enhanced by comparative analysis of the homologous structures of... 

Assemble fragments/substructures from different, known homologous structures. 

Rather than manual model building, it is possible to use a database approach to build a starting structure from homologous structural fragments taken from the crystallographic protein data bank.37 The main use of this technique is that it can be used during the earliest investigations of a molecule when adequate NMR may not yet be available. 

S. Stengelin, H. Thuring, W. Kramer, Insights into the bile add transportation system The human deal lipid-binding protein-cholyltaurine complex and its comparison with homologous structures, Proteins Struct., Funct. Genet. 2003, 50, 312-328. 

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