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1.
AcrB and its homologues are the principal multidrug transporters in Gram-negative bacteria and are important in antibiotic drug tolerance. AcrB is a homotrimer that acts as a tripartite complex with the outer membrane channel TolC and the membrane fusion protein AcrA. Minocycline and doxorubicin have been shown to bind to the phenylalanine cluster region of the binding monomer. Here we report the crystal structures of AcrB bound to the high-molecular-mass drugs rifampicin and erythromycin. These drugs bind to the access monomer, and the binding sites are located in the proximal multisite binding pocket, which is separated from the phenylalanine cluster region (distal pocket) by the Phe-617 loop. Our structures indicate that there are two discrete multisite binding pockets along the intramolecular channel. High-molecular-mass drugs first bind to the proximal pocket in the access state and are then forced into the distal pocket in the binding state by a peristaltic mechanism involving subdomain movements that include a shift of the Phe-617 loop. By contrast, low-molecular-mass drugs, such as minocycline and doxorubicin, travel through the proximal pocket without specific binding and immediately bind to the distal pocket. The presence of two discrete, high-volume multisite binding pockets contributes to the remarkably broad substrate recognition of AcrB. 相似文献
2.
Entanglement is one of the key features of quantum information and communications technology. The method that has been used most frequently to generate highly entangled pairs of photons is parametric down-conversion. Short-wavelength entangled photons are desirable for generating further entanglement between three or four photons, but it is difficult to use parametric down-conversion to generate suitably energetic entangled photon pairs. One method that is expected to be applicable for the generation of such photons is resonant hyper-parametric scattering (RHPS): a pair of entangled photons is generated in a semiconductor via an electronically resonant third-order nonlinear optical process. Semiconductor-based sources of entangled photons would also be advantageous for practical quantum technologies, but attempts to generate entangled photons in semiconductors have not yet been successful. Here we report experimental evidence for the generation of ultraviolet entangled photon pairs by means of biexciton resonant RHPS in a single crystal of the semiconductor CuCl. We anticipate that our results will open the way to the generation of entangled photons by current injection, analogous to current-driven single photon sources. 相似文献
3.
Crystal structure of bacterial multidrug efflux transporter AcrB 总被引:59,自引:0,他引:59
AcrB is a major multidrug exporter in Escherichia coli. It cooperates with a membrane fusion protein, AcrA, and an outer membrane channel, TolC. We have determined the crystal structure of AcrB at 3.5 A resolution. Three AcrB protomers are organized as a homotrimer in the shape of a jellyfish. Each protomer is composed of a transmembrane region 50 A thick and a 70 A protruding headpiece. The top of the headpiece opens like a funnel, where TolC might directly dock into AcrB. A pore formed by three alpha-helices connects the funnel with a central cavity located at the bottom of the headpiece. The cavity has three vestibules at the side of the headpiece which lead into the periplasm. In the transmembrane region, each protomer has twelve transmembrane alpha-helices. The structure implies that substrates translocated from the cell interior through the transmembrane region and from the periplasm through the vestibules are collected in the central cavity and then actively transported through the pore into the TolC tunnel. 相似文献
4.
A new species of Qianichthyosaurus Li, 1999 from the Zhuganpo Member of the Falang Formation (Ladinian, Middle Triassic), Wusha Town, Xingyi City of Guizhou is described here, namely Qianichthyosaurus xingyiensis sp. nov. The recognition of the new species revises the diagnosis of the genus: tooth size relative to the skull width slightly below 0.1; ulna peripheral “shaft” notched or largely reduced; hindlimb nearly equal or longer than forelimb; tibia peripheral “shaft” notched or largely reduced. Qianichthyosaurus xingyiensis sp. nov. differs from the type species in having relatively longer snout (snout length/skull length over 60%); humerus radial facet being prominently larger than ulnar facet; unenclosed obturator foramen on pubis; fibula posterior process on the posterior margin and the ischium sub-triangular lacking shaft. The new species is stratigraphically older than Q. zhoui, the specimens of which were exclusively known from the Wayao Member of the Falang Formation (Carnian, Late Triassic). Along with askeptosaurid thalattosaur Anshunsaurus and shastasaurid ichthyosaur Guizhouich- thyosaurus, the occurrence of Q. xingyiensis sp. nov. in Xingyi Fauna suggests a closer relationship between Xingyi Fauna (late Ladinian, Middle Triassic) and Guanling Biota (Carnian, Late Triassic). 相似文献
5.
Xing-jun LIU Cui-ping WANG Ikuo OHNUMA Ryosuke KAINUMA Kiyohito ISHIDA 《自然科学进展(英文版)》2011,21(2):97-110
Recent progress in the development of thermodynamic and kinetic databases of micro-soldering alloys,which were constructed within the framework of the Thermo-Calc and DICTRA software,was presented.Especially,a thermodynamic tool, ADAMIS(alloy database for micro-solders) was developed by combining the thermodynamic databases of micro-solders with Pandat,a multi-component phase diagram calculation software program.ADAMIS contains 11 elements,namely,Ag,Al,Au,Bi,Cu, In,Ni,Sb,Sn,Zn and Pb,and can handle all c... 相似文献
6.
Mao JH Perez-Losada J Wu D Delrosario R Tsunematsu R Nakayama KI Brown K Bryson S Balmain A 《Nature》2004,432(7018):775-779
The FBXW7/hCDC4 gene encodes a ubiquitin ligase implicated in the control of chromosome stability. Here we identify the mouse Fbxw7 gene as a p53-dependent tumour suppressor gene by using a mammalian genetic screen for p53-dependent genes involved in tumorigenesis. Radiation-induced lymphomas from p53+/- mice, but not those from p53-/- mice, show frequent loss of heterozygosity and a 10% mutation rate of the Fbxw7 gene. Fbxw7+/- mice have greater susceptibility to radiation-induced tumorigenesis, but most tumours retain and express the wild-type allele, indicating that Fbxw7 is a haploinsufficient tumour suppressor gene. Loss of Fbxw7 alters the spectrum of tumours that develop in p53 deficient mice to include a range of tumours in epithelial tissues such as the lung, liver and ovary. Mouse embryo fibroblasts from Fbxw7-deficient mice, or wild-type mouse cells expressing Fbxw7 small interfering RNA, have higher levels of Aurora-A kinase, c-Jun and Notch4, but not of cyclin E. We propose that p53-dependent loss of Fbxw7 leads to genetic instability by mechanisms that might involve the activation of Aurora-A, providing a rationale for the early occurrence of these mutations in human cancers. 相似文献
7.
AcrB is a principal multidrug efflux transporter in Escherichia coli that cooperates with an outer-membrane channel, TolC, and a membrane-fusion protein, AcrA. Here we describe crystal structures of AcrB with and without substrates. The AcrB-drug complex consists of three protomers, each of which has a different conformation corresponding to one of the three functional states of the transport cycle. Bound substrate was found in the periplasmic domain of one of the three protomers. The voluminous binding pocket is aromatic and allows multi-site binding. The structures indicate that drugs are exported by a three-step functionally rotating mechanism in which substrates undergo ordered binding change. 相似文献
8.
Road pricing policies have two equally important objectives that have to be considered: the optimal use of the road network and the fiscal sustainability for the management of the network. The aim of this work is to examine the effects on these two objectives of a recent pricing policy implemented in Japan's expressway networks. Recently the Nippon (Japan) Expressway Companies (NEXCO, operators of Japan's nation wide expressway network) have implemented several toll discount policies for users equipped with electronic toll collectors (ETCs). One of the policies is the commuter discount policy that discounts 50% for a journey on the NEXCO expressway no longer than 100 km during the commuting peak hours. This paper examines its effect on congestion reduction in the road network of Nagoya area and its influence on the use of expressways operated by another major local public expressway company in Nagoya. The congestion easing effect of this policy is compared with a potential marginal cost pricing scheme. These observations suggest that policy coordination regarding toll levels is needed for expressway corporations and transportation authorities for improving transportation efficiency of utilization of the whole network. 相似文献
9.
The photoperiodic control of flowering is one of the important developmental processes of plants because it is directly related to successful reproduction. Although the molecular genetic analysis of Arabidopsis thaliana, a long-day (LD) plant, has provided models to explain the control of flowering time in this species, very little is known about its molecular mechanisms for short-day (SD) plants. Here we show how the photoperiodic control of flowering is regulated in rice, a SD plant. Overexpression of OsGI, an orthologue of the Arabidopsis GIGANTEA (GI) gene in transgenic rice, caused late flowering under both SD and LD conditions. Expression of the rice orthologue of the Arabidopsis CONSTANS (CO) gene was increased in the transgenic rice, whereas expression of the rice orthologue of FLOWERING LOCUS T (FT) was suppressed. Our results indicate that three key regulatory genes for the photoperiodic control of flowering are conserved between Arabidopsis, a LD plant, and rice, a SD plant, but regulation of the FT gene by CO was reversed, resulting in the suppression of flowering in rice under LD conditions. 相似文献
10.
Dayong Jiang ;Ryosuke Motani ;Weicheng Hao ;Lars Schmitz ;Olivier Rieppel ;Yuanlin Sun ;Zuoyu Sun 《自然科学进展(英文版)》2008,18(10):1315-1319
A new primitive ichthyopterygian Xinminosaurus catactes gen. et. sp. nov. is erected based on a complete skeleton from the Middle Triassic Upper Member of the Guanling Formation at Panxian, Guizhou, southwestern China. It has a suite of uniquely derived char- acters in its dentition, ulna, carpals and tarsals. It is similar to primitive ichthyopterygians in retaining elongated limb bones. The new taxon and a diversity of marine reptiles in Panxian Fauna are the physical markers of the Middle Triassic Biotic radiation. Detailed studies of this fauna will supply essential knowledge on the diversity, migration and paleobiogeographic affinity of Middle Triassic ichthyopterygians. 相似文献