Structural basis for inhibition of cyclin-dependent kinase 9 by flavopiridol

Flavopiridol has been shown to potently inhibit CDK1 and 2 (cyclin-dependent kinases 1 and 2) and most recently it has been found that it also inhibits CDK9. The complex CDK9-cyclin T1 controls the elongation phase of transcription by RNA polymerase II. The present work describes a molecular model for the binary complex CDK9-flavopiridol. This structural model indicates that the inhibitor strongly binds to the ATP-binding pocket of CDK9 and the structural comparison of the complex CDK2-flavopiridol correlates the structural differences with differences in inhibition of these CDKs by flavopiridol. This structure opens the possibility of testing new inhibitor families, in addition to new substituents for the already known leading structures such as flavones and adenine derivatives. © 2002 Elsevier Science (USA). All rights reserved.

Advances in prodrug design

The background of prodrug design is presented herein as the basis for introducing new and advanced latent systems, taking into account mainly the versatility of polymers and other macromolecules as carriers. PDEPT (Polymer-Directed Enzyme Prodrug Therapy); PELT (Polymer-Enzyme Liposome Therapy); CDS (Chemical Delivery System); ADEPT(Antibody-Directed Enzyme Prodrug Therapy); GDEPT/VDEPT (Gene-Directed Enzyme Prodrug Therapy/Virus-Directed Enzyme Prodrug Therapy); ODDS (Osteotropic Drug Delivery System) and LEAPT (Lectin-directed enzyme-activated prodrug therapy) are briefly described and some examples are given. © 2005 Bentham Science Publishers Ltd.

The inhibition of 5-enolpyruvylshikimate-3-phosphate synthase as a model for development of novel antimicrobials

EPSP synthase (EPSPS) is an essential enzyme in the shikimate pathway, transferring the enolpyruvyl group of phosphoenolpyruvate to shikimate-3-phosphate to form 5-enolpyruvyl-3-shikimate phosphate and inorganic phosphate. This enzyme is composed of two domains, which are formed by three copies of βαβαββ-folding units; in between there are two crossover chain segments hinging the nearly topologically symmetrical domains together and allowing conformational changes necessary for substrate conversion. The reaction is ordered with shikimate-3-phosphate binding first, followed by phosphoenolpyruvate, and then by the subsequent release of phosphate and EPSP. N-[phosphomethyl]glycine (glyphosate) is the commercial inhibitor of this enzyme. Apparently, the binding of shikimate-3-phosphate is necessary for glyphosate binding, since it induces the closure of the two domains to form the active site in the interdomain cleft. However, it is somehow controversial whether binding of shikimate-3-phosphate alone is enough to induce the complete conversion to the closed state. The phosphoenolpyruvate binding site seems to be located mainly on the C-terminal domain, while the binding site of shikimate-3-phosphate is located primarily in the N-terminal domain residues. However, recent results demonstrate that the active site of the enzyme undergoes structural changes upon inhibitor binding on a scale that cannot be predicted by conventional computational methods. Studies of molecular docking based on the interaction of known EPSPS structures with (R)- phosphonate TI analogue reveal that more experimental data on the structure and dynamics of various EPSPS-ligand complexes are needed to more effectively apply structure-based drug design of this enzyme in the future. © 2007 Bentham Science Publishers Ltd.

Bulliform cells in Loudetiopsis chrysothrix (Nees) Conert and Tristachya leiostachya Nees (Poaceae): structure in relation to function

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Soil profile, relief features and their relation to structure and distribution of Brazilian Atlantic rain forest trees

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Surface structure and electronic properties of Pt-Fe/C nanocatalysts and their relation with catalytic activity for oxygen reduction

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Relation between antioxidant activity and electronic structure of Phenols

We describe a new physicochemical descriptor of the antioxidant activity of phenols, the energy difference between the two highest occupied molecular orbitals, which we believe will improve quantitative structure-activity relationship studies about these compounds. (C) 2003 Wiley Periodicals, Inc.

Relation between green spaces and bird community structure in an urban area in Southeast Brazil

Increased urbanization typically leads to an increase in abundance of a few species and a reduction in bird species richness. Understanding the structure of biotic communities in urban areas will allow us to propose management techniques and to decrease conflicts between wild species and human beings. The objective of this study was to describe the structure of the bird community in an urban ecosystem. The study was carried out in the city of Taubaté in southeastern Brazil. Point-counts were established in areas with different levels of tree density ranging from urban green spaces to predominantly built-up areas. We looked for a correlation between the richness/abundance of birds and the size of the area surveyed, the number of houses, the number of tree species and the number of individual trees. The results of multiple regression showed that bird richness had a direct relationship with vegetation complexity. The abundance and diversity of tree species were better predictors of bird species than the number of houses and size of the area surveyed. We discuss implications of this study for conservation and management of bird diversity in urban areas, such as the need to increase green areas containing a large diversity of native plant species. © 2011 Springer Science+Business Media, LLC.

Effect of probiotic and prebiotic inclusion in weaned piglet diets on structure and ultra-structure of small intestine

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Gochnatia polymorpha (Less.) Cabrera (Asteraceae) changes in leaf structure due to differences in light and edaphic conditions

Gochnatia polymorpha (Less.) Cabrera é uma espécie de Asteraceae com ampla distribuição no bioma cerrado, sendo encontrada em diversas fisionomias florestais da região sudeste do Brasil. O presente estudo descreve alguns caracteres anatômicos foliares dessa espécie e os analisa quantitativamente em função de sua ocorrência nas formações florestais e também das diferenças de luminosidade. Foram encontradas diferenças quantitativas em todos os parâmetros anatômicos analisados. Os resultados demonstram que a alta plasticidade anatômica foliar nesta espécie pode ser considerada como uma vantagem adaptativa que a permite ocorrer em diversos ambientes do cerrado.

Relation among optical, thermal and thermo-optical properties and niobium concentration in tellurite glasses

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Understanding the effects of isolation on seed and pollen flow, spatial genetic structure and effective population size of the dioecious tropical tree species Myracrodruon urundeuva

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

The pulvinus endodermal cells and their relation to leaf movement in legumes of the Brazilian cerrado

Legume pulvini have a clearly delimited endodermis, whose variable content has been associated with the velocity and type of leaf movement: pulvini in leaves with fast nastic movement contain starch grains; pulvini in leaves with slow nastic movements have calcium oxalate crystals as well as starch grains in the endodermis. However, the studies carried out to date have involved few legume species. This study therefore purported to examine the consistency of this hypothesis in other legumes. Thus, the structure and content of the pulvinus endodermal cells of nine legumes of the Brazilian cerrado, with different types and velocities of leaf movement, were investigated: slow nyctinastic and heliotropic movements (Bauhinia rufa, Copaifera langsdorffii, Senna rugosa - Caesalpinioideae; Andira humilis and Dalbergia miscolobium - Faboideae; Stryphnodendron polyphyllum - Mimosoideae), slow heliotropic movement (Zornia diphylla - Faboideae), and fast seismonastic and slow nyctinastic and heliotropic movements (Mimosa rixosa and Mimosa flexuosa - Mimosoideae). Samples were prepared following standard plant anatomy and ultrastructure techniques. The endodermis of all the species contains starch grains. In the species displaying only slow movements, calcium oxalate prismatic crystals were observed in addition to starch grains, except in Zornia diphylla. in conclusion, oxalate crystals occur only in endodermal cells of pulvini that display slow movements, while starch grains are always present in pulvinus endodermal cells of plants with any kind of movement.

Pulvinus functional traits in relation to leaf movements: A light and transmission electron microscopy study of the vascular system

Previous studies on legume pulvini suggest that the vascular system plays an important role in the redistribution of ions and transmission of stimuli during leaf's movements. However, the number of anatomical and ultrastructural studies is limited to few species. The aim of this paper is to investigate the structure and cellular features of the pulvinus vascular system of nine legume species from Brazilian cerrado, looking for structural traits pointing to its participation in the leaf's movements. Samples were excised from the medial region of opened pulvinus of Bauhinia rufa, Copaifera langsdorffii, Senna rugosa (Caesalpinioideae), Andira humilis, Dalbergia miscolobium, Zornia dilphylla (Faboideae), Mimosa rixosa, Mimosa flexuosa and Stryphnodendron polyphyllum (Mimosoideae), and were prepared following light microscopy, transmission electron microscopy and histochemical standard techniques. The vascular system occupies a central position, comprises phloem and xylem and is delimited by a living sheath of septate fibers in all the species studied. This living cells sheath connects the cortex to the vascular tissues via numerous plasmodesmata. The absence of fibers and sclereids, the presence of phenolic idioblasts and the abundance and diversity of protein inclusions in the sieve tube members are remarkable features of the phloem. Pitted vessel elements, parenchyma cells with abundant cytoplasm and living fibriform elements characterize the xylem. The lack of lignified tissues and extensive symplastic continuity by plasmodesmata are remarkable features of the vascular system of pulvini of the all studied species. (c) 2007 Elsevier Ltd. All rights reserved.

Crystal structure of a myotoxic Asp49-phospholipase A(2) with low catalytic activity: Insights into Ca2+ -independent catalytic mechanism

A myotoxic Asp49-phospholipase A(2) (Asp49-PLA(2)) with low catalytic activity (BthTX-II from Bothrops jararacussu venom) was crystallized and the molecular-replacement solution has been obtained with a dimer in the asymmetric unit. The quaternary structure of BthTX-II resembles the myotoxic Asp49-PLA2 PrTX-III (piratoxin III from B. pirajai venom) and all non-catalytic and myotoxic dimeric Lys49-PLA(2)s. Despite of this, BthTX-II is different from the highly catalytic and non-myotoxic BthA-I (acidic PLA(2) from B. jararacussu) and other Asp49-PLA(2)s. BthTX-II structure showed a severe distortion of calcium-binding loop leading to displacement of the C-terminal region. Tyr28 side chain, present in this region, is in an opposite position in relation to the same residue in the catalytic activity Asp49-PLA(2)s, making a hydrogen bond with the atom 0 delta 2 of the catalytically active Asp49, which should coordinate the calcium. This high distortion may also be confirmed by the inability of BthTX-II to bind Na+ ions at the Ca2+-binding loop, despite of the crystallization to have occurred in the presence of this ion. In contrast, other Asp49-PLA(2)s which are able to bind Ca2+ ions are also able to bind Na+ ions at this loop. The comparison with other catalytic, non-catalytic and inhibited PLA(2)s indicates that the BthTX-II is not able to bind calcium ions; consequently, we suggest that its low catalytic function is based on an alternative way compared with other PLA(2)s. (c) 2008 Elsevier B.V All rights reserved.