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21.
A novel peptide recognition mode revealed by the X-ray structure of a core U2AF35/U2AF65 heterodimer
U2 auxiliary factor (U2AF) is an essential splicing factor that recognizes the 3' splice site and recruits the U2 snRNP to the branch point. The X-ray structure of the human core U2AF heterodimer, consisting of the U2AF35 central domain and a proline-rich region of U2AF65, has been determined at 2.2 A resolution. The structure reveals a novel protein-protein recognition strategy, in which an atypical RNA recognition motif (RRM) of U2AF35 and the U2AF65 polyproline segment interact via reciprocal "tongue-in-groove" tryptophan residues. Complementary biochemical experiments demonstrate that the core U2AF heterodimer binds RNA, and that the interacting tryptophan side chains are essential for U2AF dimerization. Atypical RRMs in other splicing factors may serve as protein-protein interaction motifs elsewhere during spliceosome assembly. 相似文献
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Renewed debate over what benefits females might gain from producing extra‐pair offspring emphasizes the possibility that apparent differences in quality between within‐pair and extra‐pair offspring are confounded by greater maternal investment in extra‐pair offspring. Moreover, the attractiveness of a female''s social mate can also influence contributions of both partners to a reproductive attempt. Here, we explore the complexities involved in parental investment decisions in response to extra‐pair offspring and mate attractiveness with a focus on the female point of view. Adult zebra finches paired and reproduced in a colony setting. A male''s early‐life diet quality and his extra‐pair reproductive success were used as metrics of his mating attractiveness. Females paired with males that achieved extra‐pair success laid heavier eggs than other females and spent less time attending their nests than their mates or other females. Extra‐pair nestlings were fed more protein‐rich hen''s egg than within‐pair nestlings. Females producing extra‐pair offspring had more surviving sons than females producing only within‐pair offspring. Collectively, results show that females differentially allocate resources in response to offspring extra‐pair status and their social mate''s attractiveness. Females may also obtain fitness benefits through the production of extra‐pair offspring. 相似文献
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A report on the Keystone Symposium 'Meeting the Challenges of Drug Discovery', Vancouver, Canada, 15-19 January 2005. 相似文献
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Imidazolonepropionase (HutI) (imidazolone-5-propanote hydrolase, EC 3.5.2.7) is a member of the amidohydrolase superfamily and catalyzes the conversion of imidazolone-5-propanoate to N-formimino-L-glutamate in the histidine degradation pathway. We have determined the three-dimensional crystal structures of HutI from Agrobacterium tumefaciens (At-HutI) and an environmental sample from the Sargasso Sea Ocean Going Survey (Es-HutI) bound to the product [ N-formimino-L-glutamate (NIG)] and an inhibitor [3-(2,5-dioxoimidazolidin-4-yl)propionic acid (DIP)], respectively. In both structures, the active site is contained within each monomer, and its organization displays the landmark feature of the amidohydrolase superfamily, showing a metal ligand (iron), four histidines, and one aspartic acid. A catalytic mechanism involving His265 is proposed on the basis of the inhibitor-bound structure. This mechanism is applicable to all HutI forms. 相似文献
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J. William A. Burley Festus I. O. Nwoke Geoffrey L. Leister Richard A. Popham 《American journal of botany》1970,57(5):504-511
Techniques were developed to supply radioactive phosphorus to specific regions of the roots of corn and to ascertain the extent of functional xylem. The data support the view that all regions of the root are effective in absorbing phosphorus but translocation of the absorbed phosphorus to the shoot was correlated with the presence of functional xylem in the region where phosphorus was supplied. 相似文献
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David S. Goodsell Christine Zardecki Luigi Di Costanzo Jose M. Duarte Brian P. Hudson Irina Persikova Joan Segura Chenghua Shao Maria Voigt John D. Westbrook Jasmine Y. Young Stephen K. Burley 《Protein science : a publication of the Protein Society》2020,29(1):52-65
Analyses of publicly available structural data reveal interesting insights into the impact of the three‐dimensional (3D) structures of protein targets important for discovery of new drugs (e.g., G‐protein‐coupled receptors, voltage‐gated ion channels, ligand‐gated ion channels, transporters, and E3 ubiquitin ligases). The Protein Data Bank (PDB) archive currently holds > 155,000 atomic‐level 3D structures of biomolecules experimentally determined using crystallography, nuclear magnetic resonance spectroscopy, and electron microscopy. The PDB was established in 1971 as the first open‐access, digital‐data resource in biology, and is now managed by the Worldwide PDB partnership (wwPDB; wwPDB.org ). US PDB operations are the responsibility of the Research Collaboratory for Structural Bioinformatics PDB (RCSB PDB). The RCSB PDB serves millions of RCSB.org users worldwide by delivering PDB data integrated with ~40 external biodata resources, providing rich structural views of fundamental biology, biomedicine, and energy sciences. Recently published work showed that the PDB archival holdings facilitated discovery of ~90% of the 210 new drugs approved by the US Food and Drug Administration 2010–2016. We review user‐driven development of RCSB PDB services, examine growth of the PDB archive in terms of size and complexity, and present examples and opportunities for structure‐guided drug discovery for challenging targets (e.g., integral membrane proteins). 相似文献