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A novel coronavirus (2019-nCoV) outbreak has caused a global pandemic resulting in tens of thousands of infections and thousands of deaths worldwide. The RNA-dependent RNA polymerase (RdRp, also named nsp12), which catalyzes the synthesis of viral RNA, is a key component of coronaviral replication/transcription machinery and appears to be a primary target for the antiviral drug, remdesivir. Here we report the cryo-EM structure of 2019-nCoV full-length nsp12 in complex with cofactors nsp7 and nsp8 at a resolution of 2.9-[A]. Additional to the conserved architecture of the polymerase core of the viral polymerase family and a nidovirus RdRp-associated nucleotidyltransferase (NiRAN) domain featured in coronaviral RdRp, nsp12 possesses a newly identified {beta}-hairpin domain at its N-terminal. Key residues for viral replication and transcription are observed. A comparative analysis to show how remdesivir binds to this polymerase is also provided. This structure provides insight into the central component of coronaviral replication/transcription machinery and sheds light on the design of new antiviral therapeutics targeting viral RdRp. One Sentence SummaryStructure of 2019-nCov RNA polymerase.
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Objective To assess the protective effect of low melting point lead and field margin on the opposite testicular in testicular seminoma patients during postoperative radiation.Methods A patient with stage Ⅰ seminoma was selected and his phantom measurement was carried out.The PTW 0.6 cm3 type ionization chamber was used to measure the absorbed dose under the conditions of no lead and low melting point lead with thickness of 3,5,7,10 and 15 mm at different distances from the field edge,respectively.Results Under different lead thickness conditions,the measurement result and the distance between the measured points and the boundary of the field were exponentially attenuated.The relative target dose dropped from 8.41％ at 1 cm to 0.61％ at 25 cm without lead blocking,and dropped from 4.55％,3.98％ and 3.47％ at 1 cm to0.27％,0.21％ and0.17％ at 25 cm with 3,5,7 cmlead,respectively.With 10 mm lead,it dropped from 2.55％ at 1.5 cm to0.15％ at25 cm,and 1.86％ at2 cm to0.13％ at 25 cm with 15 mm lead.The lead shield of 3,7 and 15 mm thickness can be used to reduce the scatter dose of testis to below 0.5 Gy during radiotherapy for seminoma.Conclusions An appropriate thickness of low melting point lead might reduce the dose of testis conveniently and effectively,which would be beneficial to protect the fertility of the patients with testicular seminoma.
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The aspartate kinase (AK) from Mycobacterium tuberculosis (Mtb) catalyzes the biosynthesis of aspartate family amino acids, including lysine, threonine, isoleucine and methionine. We determined the crystal structures of the regulatory subunit of aspartate kinase from Mtb alone (referred to as MtbAKβ) and in complex with threonine (referred to as MtbAKβ-Thr) at resolutions of 2.6 Å and 2.0 Å, respectively. MtbAKβ is composed of two perpendicular non-equivalent ACT domains [aspartate kinase, chorismate mutase, and TyrA (prephenate dehydrogenase)] per monomer. Each ACT domain contains two α helices and four antiparallel β strands. The structure of MtbAKβ shares high similarity with the regulatory subunit of the aspartate kinase from Corynebacterium glutamicum (referred to as CgAKβ), suggesting similar regulatory mechanisms. Biochemical assays in our study showed that MtbAK is inhibited by threonine. Based on crystal structure analysis, we discuss the regulatory mechanism of MtbAK.
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Secuencia de Aminoácidos , Aspartato Quinasa , Química , Genética , Metabolismo , Sitios de Unión , Clonación Molecular , Corynebacterium glutamicum , Cristalización , Métodos , Cristalografía por Rayos X , Activación Enzimática , Pruebas de Enzimas , Escherichia coli , Genética , Metabolismo , Vectores Genéticos , Genética , Metabolismo , Lisina , Farmacología , Datos de Secuencia Molecular , Mycobacterium tuberculosis , Plásmidos , Genética , Metabolismo , Prefenato Deshidrogenasa , Metabolismo , Estructura Secundaria de Proteína , Treonina , Metabolismo , FarmacologíaRESUMEN
Three hundred cerebrovascular disease (CVD) patients (disease onset <3 days) were evaluated for serum C-reactive protein (CRP) level at admission, and Scandinavian Stroke Scale (SSS) or Oxford Handicap Scale (OHS) at baseline and 3 months. Based on serum CRP levels, the participants were divided into group A [CRP(1.20 ±0.35)mg/L], group B[CRP(4.98 ± 1.08) mg/L] or group C[CRP (19.34±12.27)mg/L]. Our results showed that serum CRP level was positively correlated with SSS (r = 0.39 or0.43, both P<0.01) and OHS (r=0.40 or0.42, both P<0.01) at3 months. Thus, evaluating serum CRP level within 3 clays of disease onset might be helpful in predicting clinical outcomes of CVD patients.
