Biomedical subjects

Ozlem Keskin

Publications and source records attributed to Ozlem Keskin.

22 records · Page 2Linked to original sources

PubMed2004

A new, structurally nonredundant, diverse data set of protein-protein interfaces and its implications.

Here, we present a diverse, structurally nonredundant data set of two-chain protein-protein interfaces derived from the PDB. Using a sequence order-independent structural comparison algorithm and hierarchical clustering, 3799 interface clusters are obtained. These yield 103 clusters with at least five nonhomologous members. We divide the clusters into three types. In Type I clusters, the global structures of the chains from which the interfaces are derived are also similar. This cluster type is expected because, in general, related proteins associate in similar ways. In Type II, the interfaces are similar; however, remarkably, the overall structures and functions of the chains are different. The functional spectrum is broad, from enzymes/inhibitors to immunoglobulins and toxins. The fact that structurally different monomers associate in similar ways, suggests "good" binding architectures. This observation extends a paradigm in protein science: It has been well known that proteins with similar structures may have different functions. Here, we show that it extends to interfaces. In Type III clusters, only one side of the interface is similar across the cluster. This structurally nonredundant data set provides rich data for studies of protein-protein interactions and recognition, cellular networks and drug design. In particular, it may be useful in addressing the difficult question of what are the favorable ways for proteins to interact. (The data set is available at http://protein3d.ncifcrf.gov/~keskino/ and http://home.ku.edu.tr/~okeskin/INTERFACE/INTERFACES.html.)

Algorithms↗

PubMed2002

Relating molecular flexibility to function: a case study of tubulin.

Microtubules (MT), along with a variety of associated motor proteins, are involved in a range of cellular functions including vesicle movement, chromosome segregation, and cell motility. MTs are assemblies of heterodimeric proteins, alpha beta-tubulins, the structure of which has been determined by electron crystallography of zinc-induced, pacilitaxel-stabilized tubulin sheets. These data provide a basis for examining relationships between structural features and protein function. Here, we study the fluctuation dynamics of the tubulin dimer with the aim of elucidating its functional motions relevant to substrate binding, polymerization/depolymerization and MT assembly. A coarse-grained model, harmonically constrained according to the crystal structure, is used to explore the global dynamics of the dimer. Our results identify six regions of collective motion, comprised of structurally close but discontinuous sequence fragments, observed only in the dimeric form, dimerization being a prerequisite for domain identification. Boundaries between regions of collective motions appear to act as linkages, found primarily within secondary-structure elements that lack sequence conservation, but are located at minima in the fluctuation curve, at positions of hydrophobic residues. Residue fluctuations within these domains identify the most mobile regions as loops involved in recognition of the adjacent regions. The least mobile regions are associated with nucleotide binding sites where lethal mutations occur. The functional coupling of motions between and within regions identifies three global motions: torsional and wobbling movements, en bloc, between the alpha- and beta-tubulin monomers, and stretching longitudinally. Further analysis finds the antitumor drug pacilitaxel (TaxotereR) to reduce flexibility in the M loop of the beta-tubulin monomer; an effect that may contribute to tightening lateral interactions between protofilaments assembled into MTs. Our analysis provides insights into relationships between intramolecular tubulin movements of MT organization and function.

Amino Acid Sequence↗

PubMed2002

Comparison of full-atomic and coarse-grained models to examine the molecular fluctuations of c-AMP dependent protein kinase.

Molecular fluctuations of the native conformation of c-AMP dependent protein kinase (cAPK) have been investigated with three different approaches. The first approach is the full atomic normal mode analysis (NMA) with empirical force fields. The second and third approaches are based on a coarse-grained model with a single single-parameter- harmonic potential between close residues in the crystal structure of the molecule without any residue specificity. The second method calculates only the magnitude of fluctuations whereas the third method is developed to find the directionality of the fluctuations which are essential to understand the functional importance of biological molecules. The aim, in this study, is to determine whether using such coarse-grained models are appropriate for elucidating the global dynamic characteristics of large proteins which reduces the size of the system at least by a factor of ten. The mean-square fluctuations of C(alpha) atoms and the residue cross-correlations are obtained by three approaches. These results are then compared to test the results of coarse grained models on the overall collective motions. All three of the approaches show that highly flexible regions correspond to the activation and solvent exposed loops, whereas the conserved residues (especially in substrate binding regions) exhibit almost no flexibility, adding stability to the structure. The anti-correlated motions of the two lobes of the catalytic core provide flexibility to the molecule. High similarities among the results of these methods indicate that the slowest modes governing the most global motions are preserved in the coarse grained models for proteins. This finding may suggest that the general shapes of the structures are representative of their dynamic characteristics and the dominant motions of protein structures are robust at coarse-grained levels.

Amino Acid Sequence↗

PubMedDate not supplied

Poppy seed allergy: a case report and review of the literature.

Seeds of the poppy plant are traditionally used in bakeries, e.g., for garnishing bread or making cakes. Reports of allergic type I sensitivity to poppy seed are rare. According to the literature, severe reactions may occur, affecting mainly patients with allergy to pollens or nuts. We report on a 16-year-old boy who has developed erythema and angioedema, conjunctivitis, and dyspnea due to inhalation of poppy seed. Skin-prick tests were positive for poppy seed, hazelnut, and chickpea. The concentration of specific IgE for poppy seed, hazelnut, and peanut were 3.36 kU/L (class 2), 1.5 kU/L (class 2), and 6.17 kU/L (class 3), respectively. Allergic reactions associated with inhalation of food allergens have been reported for some foods but not for poppy seed. This is the first report on inhalative allergy to the poppy seed. Although poppy seeds are not commonly used, we underline the possible importance of such rare and often hidden sources of allergens, especially in patients with nut allergy.

Adolescent↗