Recurrence of a binding motif?
Explore the source record for details and available documents.
Acid Anhydride Hydrolases↗
Biomedical subjects
C A Orengo
Publications and source records attributed to C A Orengo.
Comparison of conformational characteristics in structurally similar protein pairs.
Although it is known that three-dimensional structure is well conserved during the evolutionary development of proteins, there have been few studies that consider other parameters apart from divergence of the main-chain coordinates. In this study, we align the structures of 90 pairs of homologous proteins having sequence identities ranging from 5 to 100%. Their structures are compared as a function of sequence identity, including not only consideration of C alpha coordinates but also accessibility, Ooi numbers, secondary structure, and side-chain angles. We discuss how these properties change as the sequences become less similar. This will be of practical use in homology modeling, especially for modeling very distantly related or analogous proteins. We also consider how the average size and number of insertions and deletions vary as sequences diverge. This study presents further quantitative evidence that structure is remarkably well conserved in detail, as well as at the topological level, even when the sequences do not show similarity that is significant statistically.
Algorithms↗
Recurring structural motifs in proteins with different functions.
BACKGROUND: Structures that have diverged from a common ancestor often retain functional and sequence similarity, although the latter may be very reduced. Even so, the overall fold of the structure is generally highly conserved. Now however, several have been identified of proteins that have been identified that have different functions but which have converged to a similar fold. These proteins will also have low sequence identities. RESULTS: By comparing the complete structure databank against itself, using sequence and structure alignment techniques, we have been able to identify six new examples of structurally related folds that have no apparent sequence or functional similarity. These related proteins include a family of crambin-like folds and a family of ferredoxin II folds. We found that all the similarities between structures are present in small proteins and occur as motifs within the core of a larger protein. CONCLUSION: The low sequence similarity and the lack of any obvious functional relationship between proteins with similar structures suggest that the proteins have diverged from independent ancestors. The similarities may therefore be of interest for understanding the various stereochemical and physical criteria that operate to generate a favourable fold.
Journal Article↗
Identification and classification of protein fold families.
We have developed a method for identifying fold families in the protein structure data bank. Pairwise sequence alignments are first performed to extract families of homologous proteins having 35% or more sequence identity. Representatives are selected with the best resolution and R-factor to give a nonhomologous data set. Subsequent structure comparisons between all members of this set detect homologous folds with low sequence identity but highly conserved structures. By softening the requirement on structural similarity, families of analogous proteins are obtained that have related folds but more diverse structures. Representatives are selected to give a non-analogous data set. Starting with 1410 chains from the Brookhaven Data Bank, we generate a set of 150 nonhomologous folds and a set of 112 non-analogous folds. Analysis of sequence and structure conservation within the larger families shows the globins to be the most highly conserved family and the TIM barrels the most weakly conserved.
Classification↗
Fast structure alignment for protein databank searching.
A fast method is described for searching and analyzing the protein structure databank. It uses secondary structure followed by residue matching to compare protein structures and is developed from a previous structural alignment method based on dynamic programming. Linear representations of secondary structures are derived and their features compared to identify equivalent elements in two proteins. The secondary structure alignment then constrains the residue alignment, which compares only residues within aligned secondary structures and with similar buried areas and torsional angles. The initial secondary structure alignment improves accuracy and provides a means of filtering out unrelated proteins before the slower residue alignment stage. It is possible to search or sort the protein structure databank very quickly using just secondary structure comparisons. A search through 720 structures with a probe protein of 10 secondary structures required 1.7 CPU hours on a Sun 4/280. Alternatively, combined secondary structure and residue alignments, with a cutoff on the secondary structure score to remove pairs of unrelated proteins from further analysis, took 10.1 CPU hours. The method was applied in searches on different classes of proteins and to cluster a subset of the databank into structurally related groups. Relationships were consistent with known families of protein structure.
Amino Acid Sequence↗
A rapid method of protein structure alignment.
A reduction in the time required to compare two protein structures has been achieved for a previously developed structure alignment method, by reducing the number of residue pair comparisons which must be performed between the two structures. Subsets of residue pairs are selected by an iterative procedure. Initially, selection is based on similarities in solvent accessible surface areas or torsional angles or a combination of both properties, giving subsets containing approximately 2% of the total number of residue pairs. Using these subsets, a rough comparison of the two structures is generated by the structural alignment program. The information returned from this can be used to identify more accurately topologically equivalent residues in the two proteins, thus enabling a new and much smaller subset (less than 0.2% of the total number of residue pairs) to be selected. The process of iterative refinement of the residue pair subsets is repeated once more, when in 95% of the structure comparisons tested, the correct alignment of the proteins was obtained. Times required to compare the structures using the refined subsets are insignificant compared to the initial comparison, so that considerable increases in speed are possible. The method was tested on two groups of proteins, a set of remotely related alpha/beta nucleotide proteins and the variable and constant domains of the immunoglobulins. Increases in speed ranging from 50-fold to greater than 150-fold were obtained depending on the degree of similarity of the two structures. In some comparisons the alignment was improved due to the reduction in noise obtained by comparing mainly equivalent residues.
Computer Simulation↗
Regulation of the uterine epidermal growth factor receptor by estrogen.
Explore the source record for details and available documents.
Animals↗
Protein structure alignment.
A new method of comparing protein structures is described, based on distance plot analysis. It is relatively insensitive to insertions and deletions in sequence and is tolerant of the displacement of equivalent substructures between the two molecules being compared. When presented with the co-ordinate sets of two structures, the method will produce automatically an alignment of their sequences based on structural criteria. The method uses the dynamic programming optimization technique, which is widely used in the comparison of protein sequences and thus unifies the techniques of protein structure and sequence comparison. Typical structure comparison problems were examined and the results of the new method compared to the published results obtained using conventional methods. In most examples, the new method produced a result that was equivalent, and in some cases superior, to those reported in the literature.
Algorithms↗
A holistic approach to protein structure alignment.
A method of protein structure comparison developed previously is extended to incorporate other aspects of protein structure in addition to the inter-atomic vectors on which it was originally based. Each additional aspect, which induced hydrogen bonding, solvent exposure, torsional angles and sequence, was introduced separately and evaluated for its ability to improve alignment quality. The components were then combined, suitably weighted, to produce a more holistic comparison method. The method was tested on a group of remotely related beta/alpha type proteins that share a common feature in their overall chain fold. The results indicated that while the original inter-atomic vector component was sufficient to give the correct alignment of most pairs of topologically equivalent proteins, the inclusion of hydrogen bonds, torsion angles and a measure of solvent exposure led to improvements in the more difficult comparisons. Consideration of amino acid properties, including hydrophobicity, had no beneficial effect. The failure of the latter component was not unexpected considering the almost total lack of sequence similarity among the proteins considered.
Chemistry, Physical↗
Interactions between estrogen and EGF in uterine growth and function.
The rat uterus contains specific, high-affinity EGF receptors which possess a tyrosine kinase activity. As demonstrated autoradiographically, these receptors are present in the epithelial, stromal and myometrial cells of the uterus. Estrogen treatment in vivo produces a 2-3-fold increase in EGF receptor levels in the immature rat, the immature mouse and the ovariectomized adult rat; furthermore, EGF receptor levels vary throughout the estrus cycle in concert with levels of occupied nuclear estrogen receptor. This estrogen-induced increase in EGF receptor is preceded by an increase in the level of EGF receptor mRNA as judged by Northern blot analysis. In general, there is a good correlation between estrogen-induced DNA synthesis and EGF receptor levels in the uterus, although in certain situations EGF receptor levels are elevated without a subsequent increase in DNA synthesis. These observations suggest that an increase in tissue EGF receptor levels is important in estrogen-induced uterine growth, but that this increase in receptor levels alone is not sufficient to stimulate DNA synthesis. In addition to its possible role in tissue growth, we have shown very recently that EGF causes contraction of myometrial smooth muscle in a completely in vitro organ bath system. The qualitative nature of this contractile response is distinct from that produced by other classical uterotonic agents. The physiological significance of this uterine response to EGF remains to be elucidated.
Animals↗
Review: what can structural classifications reveal about protein evolution?
In this article we present a review of the methods used for comparing and classifying protein structures. We discuss the hierarchies and populations of fold groups and evolutionary families in some of the major classifications and we consider some of the problems confronting any general analyses of structural evolution in protein families. We also review some more recent analyses that have expanded these classifications by identifying sequence relatives in the genomes and thereby reveal interesting trends in fold usage and recurrence.
Animals↗
Functional impairment in COPD patients: the impact of anxiety and depression.
The authors examined the relationship between functional status and comorbid anxiety and depression and the relationship between utilization of health care resources and psychopathology in elderly patients with chronic obstructive pulmonary disease (COPD). Elderly male veterans (N = 43) with COPD completed anxiety, depression, and functional status measures. The authors constructed regression models to explore the contribution of COPD severity, medical burden, depression, and anxiety to the dependent variables of functional impairment and health care utilization. Anxiety and depression contributed significantly to the overall variance in functional status of COPD patients, over and above medical burden and COPD severity, as measured by the 8 scales of the Medical Outcomes Study (MOS) 36-item Short Form Health Survey. Surprisingly, medical burden and COPD severity did not contribute significantly to overall variance in functional status. Few patients were receiving any treatment for anxiety or depression.
Activities of Daily Living↗