Abstract:
:Dimerization of human immunodeficiency virus type 1 protease (HIV-1 PR) monomers is an essential prerequisite for viral proteolytic activity and the subsequent generation of infectious virus particles. Disruption of the dimer interface inhibits this activity as does formation of heterodimers between wild-type and defective monomers. A structure-based approach was used to identify amino acid substitutions at the dimer interface of HIV-1 PR that facilitate preferential association of heterodimers and inhibit self-association of the defective monomers. Expression of the designed PR monomers inhibits activity of wild-type HIV-1 PR and viral infectivity when assayed in an ex vivo model system. These results show that it is possible to design PR monomers as macromolecular inhibitors that may provide an alternative to small molecule inhibitors for the treatment of HIV infection.
journal_name
Proc Natl Acad Sci U S Aauthors
McPhee F,Good AC,Kuntz ID,Craik CSdoi
10.1073/pnas.93.21.11477subject
Has Abstractpub_date
1996-10-15 00:00:00pages
11477-81issue
21eissn
0027-8424issn
1091-6490journal_volume
93pub_type
杂志文章abstract::Scientific and engineering innovation is vital for American competitiveness, quality of life, and national security. However, too few American students, especially women, pursue these fields. Although this problem has attracted enormous attention, rigorously tested interventions outside artificial laboratory settings ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1613117114
更新日期:2017-06-06 00:00:00
abstract::Phages of the Caudovirales order possess a tail that recognizes the host and ensures genome delivery upon infection. The X-ray structure of the approximately 1.8 MDa host adsorption device (baseplate) from the lactococcal phage TP901-1 shows that the receptor-binding proteins are pointing in the direction of the host,...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1200966109
更新日期:2012-06-05 00:00:00
abstract::A site that is preferentially cleaved by the single-strand-specific endonuclease from Aspergillus oryzae was located in vitro 180 base pairs upstream from the 5' end of the chicken pro-alpha 2(I) collagen gene. It is found in supercoiled plasmids with a negative superhelical density of -0.024 or more but not in linear...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.81.6.1659
更新日期:1984-03-01 00:00:00
abstract::What are the origins of humans' capacity to represent social relations? We approached this question by studying human infants' understanding of social dominance as a stable relation. We presented infants with interactions between animated agents in conflict situations. Studies 1 and 2 targeted expectations of stabilit...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1113194109
更新日期:2012-05-01 00:00:00
abstract::Climate warming is expected to mobilize northern permafrost and peat organic carbon (PP-C), yet magnitudes and system specifics of even current releases are poorly constrained. While part of the PP-C will degrade at point of thaw to CO2 and CH4 to directly amplify global warming, another part will enter the fluvial ne...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1811797116
更新日期:2019-05-21 00:00:00
abstract::The nucleosomal repeat lengths of bulk chromatin and the chromatin of transcriptionally active and inactive genes were analyzed in two mouse cell lines and adult mouse spleens. The adult beta-globin gene exhibits a nucleosomal repeat length approximately 11 base pairs longer than (i) an inactive embryonic globin gene,...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.80.18.5505
更新日期:1983-09-01 00:00:00
abstract::Psychedelic drugs have a long history of use in healing ceremonies, but despite renewed interest in their therapeutic potential, we continue to know very little about how they work in the brain. Here we used psilocybin, a classic psychedelic found in magic mushrooms, and a task-free functional MRI (fMRI) protocol desi...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 临床试验,杂志文章
doi:10.1073/pnas.1119598109
更新日期:2012-02-07 00:00:00
abstract::A human beta-globin gene derived from an established human lymphoblast cell line was introduced into murine erythroleukemia (MEL) cells by cell fusion. The globin genes in MEL cells are inducible by dimethyl sulfoxide (Me2SO); induction leads to the accumulation of mouse globin mRNA and hemoglobin. Globin mRNA was not...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.77.6.3435
更新日期:1980-06-01 00:00:00
abstract::The Escherichia coli flagellar motor senses the intracellular concentration of the response regulator CheY-P and responds by varying the bias between its counterclockwise (CCW) and clockwise (CW) rotational states. The response is ultrasensitive with a large Hill coefficient (approximately 10). Recently, the detailed ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0804641105
更新日期:2008-08-19 00:00:00
abstract::The 16S rRNA genes of Pyrobaculum aerophilum and Pyrobaculum islandicum were amplified by the polymerase chain reaction, and the resulting products were sequenced directly. The two organisms are closely related by this measure (over 98% similar). However, they differ in that the (lone) 16S rRNA gene of Pyrobaculum aer...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.90.6.2547
更新日期:1993-03-15 00:00:00
abstract::The Japanese firefly squid, Watasenia scintillans, emits intense flashes of light from three tiny luminous organs that are located at the tip of each of a pair of ventral arms. Light is also produced from hundreds of other minute organs that are scattered over the body. The luminescence is due to an ATP-dependent reac...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.82.14.4629
更新日期:1985-07-01 00:00:00
abstract::Although mathematical models and laboratory experiments have shown that species interactions can generate chaos, field evidence of chaos in natural ecosystems is rare. We report on a pristine rocky intertidal community located in one of the world's oldest marine reserves that has displayed a complex cyclic succession ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1421968112
更新日期:2015-05-19 00:00:00
abstract::We obtain a collection of multilinear Littlewood-Paley estimates, which we then apply to two problems in partial differential equations. The first problem is the estimation of the square root of an elliptic operator in divergence form, and the second is the estimation of solutions to the Cauchy problem for nondivergen...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.79.18.5746
更新日期:1982-09-01 00:00:00
abstract::We quantitatively analyzed, using laser scanning confocal microscopy, the three-dimensional structure of individual senile plaques in Alzheimer disease. We carried out the quantitative analysis using statistical methods to gain insights about the processes that govern Abeta peptide deposition. Our results show that pl...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.94.14.7612
更新日期:1997-07-08 00:00:00
abstract::Tauopathies are a class of neurodegenerative diseases associated with pathological tau. Despite many advances in our understanding of these diseases, the direct mechanism through which tau contributes to neurodegeneration remains poorly understood. Previously, our laboratory implicated the histone demethylase LSD1 in ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.2013552117
更新日期:2020-11-17 00:00:00
abstract::Glyco-immune checkpoint receptors, molecules that inhibit immune cell activity following binding to glycosylated cell-surface antigens, are emerging as attractive targets for cancer immunotherapy. Defining biologically relevant ligands that bind and activate such receptors, however, has historically been a significant...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.2015024118
更新日期:2021-02-02 00:00:00
abstract::The visual images in the eyes contain much more information than the brain can process. An important selection mechanism is feature-based attention (FBA). FBA is best described by attention filters that specify precisely the extent to which items containing attended features are selectively processed and the extent to...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1614062113
更新日期:2016-10-25 00:00:00
abstract::This paper reports a general in situ method to grow a polymer conjugate solely from the C terminus of a recombinant protein. GFP was fused at its C terminus with an intein; cleavage of the intein provided a unique thioester moiety at the C terminus of GFP that was used to install an atom transfer radical polymerizatio...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1006044107
更新日期:2010-09-21 00:00:00
abstract::Point mutations in vascular smooth muscle α-actin (SM α-actin), encoded by the gene ACTA2, are the most prevalent cause of familial thoracic aortic aneurysms and dissections (TAAD). Here, we provide the first molecular characterization, to our knowledge, of the effect of the R258C mutation in SM α-actin, expressed wit...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1507587112
更新日期:2015-08-04 00:00:00
abstract::The Arabidopsis thaliana SOS2 and SOS3 genes are required for intracellular Na(+) and K(+) homeostasis and plant tolerance to high Na(+) and low K(+) environments. SOS3 is an EF hand type calcium-binding protein having sequence similarities with animal neuronal calcium sensors and the yeast calcineurin B. SOS2 is a se...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.040577697
更新日期:2000-03-28 00:00:00
abstract::A broad program of freezing species in threatened ecospheres could preserve biodiversity for eventual use by future generations. Sampling without studying can lower costs dramatically. Local labor can do most of the gathering. Plausible costs of collecting and cryogenically suspending the tropical rain forest species,...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.89.22.11098
更新日期:1992-11-15 00:00:00
abstract::The ras oncogene products require membrane localization for their function, and this is thought to be accomplished by the addition of a palmitoyl group to a cysteine residue near the carboxyl terminus of the nascent chain. A lipidated carboxyl-terminal cysteine residue is also found in sequence-related yeast sex facto...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.85.13.4643
更新日期:1988-07-01 00:00:00
abstract::We have previously observed the spontaneous, pH-dependent insertion of a water-soluble peptide to form a helix across lipid bilayers [Hunt, J. F., Rath, P., Rothschild, K. J. & Engelman, D. M. (1997) Biochemistry 36, 15177-15192]. We now use a related peptide, pH (low) insertion peptide, to translocate cargo molecules...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0601463103
更新日期:2006-04-25 00:00:00
abstract::In recent years, a large body of research has demonstrated that judgments and behaviors can propagate from person to person. Phenomena as diverse as political mobilization, health practices, altruism, and emotional states exhibit similar dynamics of social contagion. The precise mechanisms of judgment propagation are ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1611998114
更新日期:2017-04-18 00:00:00
abstract::The ability to track cells and their patterns of gene expression in living organisms can increase our understanding of tissue development and disease. Gene reporters for bioluminescence, fluorescence, radionuclide, and magnetic resonance imaging (MRI) have been described but these suffer variously from limited depth p...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1319000111
更新日期:2014-01-07 00:00:00
abstract::To determine which of seven library design algorithms best introduces new protein function without destroying it altogether, seven combinatorial libraries of green fluorescent protein variants were designed and synthesized. Each was evaluated by distributions of emission intensity and color compiled from measurements ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0609647103
更新日期:2007-01-02 00:00:00
abstract::We have constructed an opal suppressor system in Escherichia coli to complement an existing amber suppressor system to study the structural basis of tRNA acceptor identity, particularly the role of middle anticodon nucleotide at position 35. The opal suppressor tRNA contains a UCA anticodon and the mRNA of the suppres...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.87.23.9260
更新日期:1990-12-01 00:00:00
abstract::Highly purified globin mRNA from ducks was copied with RNA-directed DNA polymerase from avian myeloblastosis virus into anti-messenger DNA. With excess RNA, more than 90% of this DNA annealed back to its template with a C(o)t/2 value of 7.5 x 10(-4) mol.sec. liter(-1); the melting temperature of the hybrid was 86 degr...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.70.4.1122
更新日期:1973-04-01 00:00:00
abstract::After prolonged visual adaptation of Drosophila, dramatic long-term changes of in vitro phosphorylation of a 50-kDa brain protein that is identical to the Ca2+/calmodulin-dependent protein kinase (EC 2.7.1.37) can be measured in isolated heads. By selective receptor cell desensitization in blue light, subcellular dist...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.83.24.9789
更新日期:1986-12-01 00:00:00
abstract::Rapid electrical conduction in the His-Purkinje system tightly controls spatiotemporal activation of the ventricles. Although recent work has shed much light on the regulation of early specification and morphogenesis of the His-Purkinje system, less is known about how transcriptional regulation establishes impulse con...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1106911108
更新日期:2011-08-16 00:00:00