Abstract:
:A descriptive medium for the presentation of protein structure has been developed and used to evaluate the structure of the active site of bovine trypsin (EC 3.4.21.4). This technique, involving advanced computer graphics technology, permits the facile display of a representation of the molecular surface of proteins of known structure and employs color to code the structural or chemical features of this surface. Benzamidine derivatives were inserted into the benzamidine-binding site of trypsin and the binary inhibitor-trypsin complex was evaluated by using the computer-generated structure. On the basis of qualitative assessments of the contribution of electrostatic and hydrophobic forces to the binding energy associated with complex formation, we made predictions concerning the effects of interaction of benzamidine substituents and amino acid side chains upon the binding energy associated with inhibitor-protein binding. The computer display of the molecular surfaces of the binary complex of substituted benzamidines and trypsin permitted unique insight into the identity and chemical properties of the atoms that participate at the interface of the molecular surfaces of the inhibitor and the protein. The computer-generated molecular surface display can potentially be combined with quantitative definition of the physical forces involved in the interaction of molecular surfaces. This technology should facilitate the study of the structure-activity relationship of substrates, inhibitors, and drugs that bind to proteins of known three-dimensional structure.
journal_name
Proc Natl Acad Sci U S Aauthors
Feldmann RJ,Bing DH,Furie BC,Furie Bdoi
10.1073/pnas.75.11.5409subject
Has Abstractpub_date
1978-11-01 00:00:00pages
5409-12issue
11eissn
0027-8424issn
1091-6490journal_volume
75pub_type
杂志文章abstract::The cingulate gyri in 37 subjects with and without early dementia of the Alzheimer type (DAT) were studied by using MRI at 1.0 mm3 isotropic resolution. Groups were segregated into young controls (n = 10), age-matched normal controls (n = 10), very mild DAT (n = 8), and mild DAT (n = 9). By using automated Bayesian 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.2136624100
更新日期:2003-12-09 00:00:00
abstract::The proteinase-activated receptor 2 (PAR-2) is a member of a family of G protein-coupled receptors for proteases. Proteases cleave PARs within the extracellular N-terminal domains to expose tethered ligands that bind to and activate the cleaved receptors. PAR-2 is highly expressed in colon in epithelial and neuronal e...
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.241377298
更新日期:2001-11-20 00:00:00
abstract::When we grasp and manipulate an object, populations of tactile nerve fibers become activated and convey information about the shape, size, and texture of the object and its motion across the skin. The response properties of tactile fibers have been extensively characterized in single-unit recordings, yielding importan...
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.1704856114
更新日期:2017-07-11 00:00:00
abstract::CD4-expressing T cells in lymphoid organs are infected by the primary strains of HIV and represent one of the main sources of virus replication. Gene therapy strategies are being developed that allow the transfer of exogenous genes into CD4(+) T lymphocytes whose expression might prevent viral infection or replication...
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.94.16.8640
更新日期:1997-08-05 00:00:00
abstract::In a primitive chordate model of natural chimerism, one chimeric partner is often eliminated in a process of allogeneic resorption. Here, we identify the cellular framework underlying loss of tolerance to one partner within a natural Botryllus schlosseri chimera. We show that the principal cell type mediating chimeric...
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.1606276113
更新日期:2016-06-07 00:00:00
abstract::Exposure of receptor-rich membrane fragments from Torpedo marmorata to carbamylcholine causes a slow (half-time of 5--10 min) and reversible change of properties of the cholinergic receptor protein manifested by a decrease of the initial rate of Naja nigricollis alpha-[3H]toxin binding in the presence of carbamylcholi...
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.72.9.3443
更新日期:1975-09-01 00:00:00
abstract::It is shown that initiation of translation involves several steps. (i) Binding of fMet-tRNA(fMet) to the bacterial 30S ribosomal subunit in the absence of messenger RNA, yielding a 34S complex. This binding is rapid and dependent on initiation factor 2 but not on initiation factor 3. (ii) Binding of messenger RNA to t...
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.71.8.3199
更新日期:1974-08-01 00:00:00
abstract::Clinical research should conform to high standards of ethical and scientific integrity, given that human lives are at stake. However, economic incentives can generate conflicts of interest for investigators, who may be inclined to withhold unfavorable results or even tamper with data in order to achieve desired outcom...
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.1919906117
更新日期:2020-06-16 00:00:00
abstract::We have isolated a 2.7-kilobase rat liver cDNA clone that contains the entire 544-amino acid coding sequence for matrin F/G. This protein has previously been localized to the internal, fibrogranular areas of the nuclear matrix and shown to bind to DNA on nitrocellulose blots. The predicted amino acid sequence from the...
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.88.14.6186
更新日期:1991-07-15 00:00:00
abstract::Ethylenediaminetetraacetic acid and diethylenetriaminepentaacetic acid have been attached covalently to the 5' terminus of the deoxynucleotide sequence C-A-C-A-A-T-T-C-C-A-C-A-C-A-A-C (16-mer) via an ethylenediamine linker. In the presence of Fe2+ and dithiothreitol, these reagents bring about the hybridization-depend...
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.82.4.963
更新日期:1985-02-01 00:00:00
abstract::Whereas several apoptosis-related proteins have been linked to the antiapoptotic effects of Akt serine-threonine kinase, the search continues to explain the Akt signaling role in promoting cell survival via antiapoptotic effects. Here, we demonstrate that Akt phosphorylates the androgen receptor (AR) at Ser-210 and 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.121173298
更新日期:2001-06-19 00:00:00
abstract::Double-positive (DP) thymocytes respond to intrathymic T-cell receptor (TCR) signals by undergoing positive selection and lineage differentiation into single-positive (SP) mature cells. Concomitant with these well-characterized events is the acquisition of a mature T-cell gene expression program characterized by the i...
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.1617669114
更新日期:2017-01-03 00:00:00
abstract::A method is described in which the interference of radiated second-harmonic electric fields generated by a pair of oriented molecules intercalated into double-stranded DNA is controlled and measured. The results show that the relative molecular orientation of the two molecules significantly changes the magnitude of th...
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.1302554110
更新日期:2013-04-09 00:00:00
abstract::Many marine bacteria have evolved to grow optimally at either high (copiotrophic) or low (oligotrophic) nutrient concentrations, enabling different species to colonize distinct trophic habitats in the oceans. Here, we compare the genome sequences of two bacteria, Photobacterium angustum S14 and Sphingopyxis alaskensis...
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.0903507106
更新日期:2009-09-15 00:00:00
abstract::AcrAB is a constitutively expressed, major multidrug efflux system of Escherichia coli. We have purified the cytoplasmic membrane component, AcrB, to near homogeneity, and reconstituted the protein into proteoliposomes. In the presence of DeltapH (outside acid), the protein catalyzed the extrusion of fluorescent phosp...
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.96.13.7190
更新日期:1999-06-22 00:00:00
abstract::The temporal dynamics of electrical activity in an olfactory organ, the procerebral lobe of the terrestrial mollusc Limax maximus, is studied. The lobe exhibits intrinsic oscillations in its field potential. Intracellular recordings show that the lobe contains two classes of neurons, both with activity phase-locked 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.91.2.669
更新日期:1994-01-18 00:00:00
abstract::Mutagenesis of protein-encoding sequences occurs ubiquitously; it enables evolution, accumulates during aging, and is associated with disease. Many biotechnological methods exploit random mutations to evolve novel proteins. To quantitate protein tolerance to random change, it is vital to understand the probability tha...
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.0403255101
更新日期:2004-06-22 00:00:00
abstract::Ice-core records show that climate changes in the past have been large, rapid, and synchronous over broad areas extending into low latitudes, with less variability over historical times. These ice-core records come from high mountain glaciers and the polar regions, including small ice caps and the large ice sheets of ...
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.97.4.1331
更新日期:2000-02-15 00:00:00
abstract::Previous studies have shown that in mammalian cells proteins of large molecular weight are degraded more rapidly than small ones. Evidence is presented here that half-lives of proteins are also related to their isoelectric points. A double-isotope method was used to compare degradative rates of soluble proteins separa...
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.72.10.3893
更新日期:1975-10-01 00:00:00
abstract::We image macroscopic transient pores in mechanically stretched giant vesicles. Holes open above a critical radius r(c1), grow up to a radius r(c2), and close. We interpret the upper limit r(c2) by a relaxation of the membrane tension as the holes expand. The closing of the holes is caused by a further relaxation of th...
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.96.19.10591
更新日期:1999-09-14 00:00:00
abstract::Four polyimidazoles were used in the binding and cleavage studies with poly(U). The two polydisperse polyvinylimidazoles were previously described by others, while the other two new polymers of polyethyleneimines were prepared by cationic polymerization of oxazolines. The latter had imidazole units attached to each ni...
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.1210846109
更新日期:2012-08-07 00:00:00
abstract::Depressed contractile function plays a primary role in the pathophysiology of acute myocardial ischemia. Intracellular acidification is an important factor underlying the inhibition of force production in the ischemic myocardium. The effect of acidosis to depress contractility is markedly greater in cardiac as compare...
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.90.19.9036
更新日期:1993-10-01 00:00:00
abstract::Human mammary epithelial cells secrete and express on their cell surfaces complex mucin glycoproteins (Mr greater than 250,000) that are developmentally regulated, tumor-associated, and highly immunogenic. Studies using monoclonal antibodies directed to these glycoproteins suggest that their molecular structures can v...
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.84.17.6060
更新日期:1987-09-01 00:00:00
abstract::A series of monoclonal antibodies was used to define three discrete stages of human intrathymic T-cell differentiation. The earliest stage was confined to <10% of thymocytes, which were.reactive with both OKT9 and OKT10. Subsequently, approximately 70% of human thymocytes acquired a thymocyte-restricted antigen, OKT6,...
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.77.3.1588
更新日期:1980-03-01 00:00:00
abstract::cDNA clones corresponding to the polypeptide that has been shown to be an endogenous diazepam binding inhibitor and may act as a physiological ligand for the benzodiazepine/beta-carboline receptor have been isolated from bacteriophage lambda recombinant libraries from rat hypothalamus, total brain, and liver. The clon...
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.83.19.7221
更新日期:1986-10-01 00:00:00
abstract::Because of increased numbers of recorded pertussis cases in the United States, this study sought to understand the role of nonmedical vaccine exemptions and waning immunity may have had on the resurgence of pertussis in the United States at the community level. We used geospatial scan statistics, SaTScan, version 9.4,...
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.1700240114
更新日期:2017-07-03 00:00:00
abstract::Cellular membranes are a heterogeneous mix of lipids, proteins and small molecules. Special groupings enriched in saturated lipids and cholesterol form liquid-ordered domains, known as "lipid rafts," thought to serve as platforms for signaling, trafficking and material transport throughout the secretory pathway. Quest...
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.0903825106
更新日期:2009-08-11 00:00:00
abstract::Thymic epithelial cells (TECs), the major component of the thymic microenvironment, can be modulated by pituitary hormones. We have shown previously that prolactin (PRL) can influence the endocrine activity of TECs and stimulate TEC proliferation as well as cytokeratin expression, suggesting the existence of PRL recep...
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.88.21.9700
更新日期:1991-11-01 00:00:00
abstract::The gamma-aminobutyrate-synthesizing enzyme glutamate decarboxylase (GAD; L-glutamate 1-carboxy-lyase, EC 4.1.1.15) is a major target of autoantibodies associated with both early and late stages of pancreatic beta-cell destruction and development of type 1 diabetes. We have used five monoclonal anti-islet-cell antibod...
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.90.7.2832
更新日期:1993-04-01 00:00:00
abstract::Leukocytes normally marginate toward the vascular wall in large vessels and within the microvasculature. Reversal of this process, leukocyte demargination, leads to substantial increases in the clinical white blood cell and granulocyte count and is a well-documented effect of glucocorticoid and catecholamine hormones,...
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.1508920113
更新日期:2016-02-23 00:00:00