Based on the crystal symmetry of [L-Met]^(B0) bovine insulin (LMBBI) and the fundamental theory of the molecular packing method, the scheme for the determination of the position and orientation of the molecules by onl...Based on the crystal symmetry of [L-Met]^(B0) bovine insulin (LMBBI) and the fundamental theory of the molecular packing method, the scheme for the determination of the position and orientation of the molecules by only using one-dimensional rotation and one-dimensional translation was chosen to be used,and therefore the calculation of the rotation function of the molecular replacement method and the refinement of the rotational and translational parameters by using the R-factor search method were simplified greatly. After the preliminary refinement by using the macromolecular rigid body refinement technique, the molecular model was further refined and adjusted by using the energy-minimizing stereochemical-restrained least squares refinement technique assisted by the manual revision on the difference Fourier maps.The L-Met residues on the N-termlnus of the B-chain appeared clearly on the final electron density map.展开更多
Subtilisin secreted from a variety of Bacillus species is an alkaline protease. The peptide-chain folding of this kind of enzyme is totally different from the mammalian serine protease, but their catalytic residues ar...Subtilisin secreted from a variety of Bacillus species is an alkaline protease. The peptide-chain folding of this kind of enzyme is totally different from the mammalian serine protease, but their catalytic residues are the same and have almost identical space arrangement, so they belong to different kinds of serine proteases. The structure and function of subtilisin have been studied extensively. Subtilisin also has some other advantages for protein engineering studies and is an important industrial enzyme which is mass-used as a component of synthetic detergent to degrade proteins. Therefore a展开更多
Desheptapeptide (B24 B30) insulin (DHPI), a virtually inactive insulin analog, has been crystallized in space group P2\-12\-12\-1 with two DHPI molecules in an asymmetric unit. The orientations and positions of the mo...Desheptapeptide (B24 B30) insulin (DHPI), a virtually inactive insulin analog, has been crystallized in space group P2\-12\-12\-1 with two DHPI molecules in an asymmetric unit. The orientations and positions of the molecules were determined by molecular replacement, and a structural model was built at 0.3 nm resolution. The current model shows that the two DHPI monomers are related by a non crystallographic 2 fold axis, nearly parallel to the crystallographic c axis. This structural feature complicated the determination of the orientation of the local 2 fold axis, which was later confirmed by analysing the diffraction data of DHPI crystals.展开更多
A previously published new rotation function has been improved by using a dynamic correlation coefficient as well as two new scoring functions of relative entropy and mean-square-residues to make the rotation function...A previously published new rotation function has been improved by using a dynamic correlation coefficient as well as two new scoring functions of relative entropy and mean-square-residues to make the rotation function more robust and independent of a specific set of weights for scoring and ranking. The previously described new rotation function calculates the rotation function of molecular replacement by matching the search model directly with the Patterson vector map. The signal-to-noise ratio for the correct match was increased by averaging all the matching peaks. Several matching scores were employed to evaluate the goodness of matching. These matching scores were then combined into a single total score by optimizing a set of weights using the linear regression method. It was found that there exists an optimal set of weights that can be applied to the global rotation search and the correct solution can be ranked in the top 100 or less. However, this set of optimal weights in general is dependent on the search models and the crystal structures with different space groups and cell parameters. In this work, we try to solve this problem by designing a dynamic correlation coefficient. It is shown that the dynamic correlation coefficient works for a variety of space groups and cell parameters in the global search of rotation function. We also introduce two new matching scores： relative entropy and mean-square-residues. Last but not least, we discussed a valid method for the optimization of the adjustable parameters for matching vectors.展开更多
From the conventional knowledge of protein nutrition to the molecular nutrition of amino acids, our understanding of protein/amino acid nutrition is rapidly increasing. Amino acids control cell growth and metabolism t...From the conventional knowledge of protein nutrition to the molecular nutrition of amino acids, our understanding of protein/amino acid nutrition is rapidly increasing. Amino acids control cell growth and metabolism through two amino acid-sensingpathways, i.e. target of rapamycin complex 1 (TORC1) and the general control nonderepressible 2 (GCN2) signaling pathway.In the amino acid-abundant status, TORC1 dominates intracellular signaling and increases protein synthesis and cell growth.In contrast, amino acid deprivation actives GCN2 resulting in repression of general protein synthesis but facilitates the aminoacid transport and synthesis process. By integrating and coordinating nutrition and hormone signaling, TORC1 and GCN2control the switch of the catabolism and anabolism phase in most eukaryotes. Now, we appreciate that the availability ofindividual amino acids is sensed by intracellular sensors. These cutting-edge findings expand our knowledge of amino acidnutrition. Although the TORC1 and GCN2 were discovered decades ago, the study of molecular amino acid nutrition inaquaculture animals is still at its infancy. The aquaculture industry is highly dependent on the supply of fishmeal, which isthe major protein source in aquacultural animal diets. Some concerted efforts were conducted to substitute for fishmeal dueto limited supply of it. However, the concomitant issues including the unbalanced amino acid profile of alternative proteinsources limited the utilization of those proteins. Continued study of the molecular nutrition of amino acid in aquacultureanimals may be expected in the immediate future to expand our knowledge on the utilization of alternative protein sources.展开更多
目的比较利伐沙班片和低分子肝素钙注射液预防老年关节置换术后下肢深静脉血栓的临床疗效。方法选取2015年2月—2016年5月天津港口医院收治的关节置换术患者120例为研究对象,所有患者根据用药方案不同分为低分子肝素组(64例)和利伐沙班...目的比较利伐沙班片和低分子肝素钙注射液预防老年关节置换术后下肢深静脉血栓的临床疗效。方法选取2015年2月—2016年5月天津港口医院收治的关节置换术患者120例为研究对象,所有患者根据用药方案不同分为低分子肝素组(64例)和利伐沙班组(56例)。低分子肝素组术后皮下注射低分子肝素钙注射液,0.2 m L/次,1次/d,第3天后剂量调整为0.4 m L/d。利伐沙班组术后口服利伐沙班片,10 mg/次,1次/d。两组患者连续治疗10 d。比较观察两组的深静脉血栓发生率、术中失血量、血液相关指标和血栓弹力图(TEG)。结果治疗后,两组深静脉血栓发生率比较差异无统计学意义。在关节置换手术中,两组术中总失血量和显性失血量比较差异无统计学意义。术后2、4 d,两组血红蛋白、血小板计数、PT和APTT比较差异无统计学意义。术后2、4 d,利伐沙班组D-二聚体(D-D)和纤维蛋白降解产物(FDP)显著低于低分子肝素组,国际标准化比值(INR)显著高于低分子肝素组,两组比较差异具有统计学意义(P<0.05)。术后2 d,利伐沙班组凝血因子反应时间(R)、血凝块成形时间(K)显著高于低分子肝素组,描记图最大曲线弧度作切线与水平线的夹角(Angle)、最大振幅(MA)和综合凝血指数(CI)显著低于低分子肝素组,两组比较差异具有统计学意义(P<0.05)。在治疗期间,低分子肝素组和利伐沙班组不良反应总发生率分别为46.88%、37.50%,两组比较差异具有统计学意义(P<0.05)。结论利伐沙班片预防老年关节置换术后下肢深静脉血栓优于低分子肝素钙注射液,可降低血液高凝状态,安全性较好,具有一定的临床推广应用价值。展开更多
基金Project supported by the National Natural Science Foundation of China and the Bureau of Biology, Academia Sinica.
文摘Based on the crystal symmetry of [L-Met]^(B0) bovine insulin (LMBBI) and the fundamental theory of the molecular packing method, the scheme for the determination of the position and orientation of the molecules by only using one-dimensional rotation and one-dimensional translation was chosen to be used,and therefore the calculation of the rotation function of the molecular replacement method and the refinement of the rotational and translational parameters by using the R-factor search method were simplified greatly. After the preliminary refinement by using the macromolecular rigid body refinement technique, the molecular model was further refined and adjusted by using the energy-minimizing stereochemical-restrained least squares refinement technique assisted by the manual revision on the difference Fourier maps.The L-Met residues on the N-termlnus of the B-chain appeared clearly on the final electron density map.
基金Project supported by the National High-Tech. Program of China.
文摘Subtilisin secreted from a variety of Bacillus species is an alkaline protease. The peptide-chain folding of this kind of enzyme is totally different from the mammalian serine protease, but their catalytic residues are the same and have almost identical space arrangement, so they belong to different kinds of serine proteases. The structure and function of subtilisin have been studied extensively. Subtilisin also has some other advantages for protein engineering studies and is an important industrial enzyme which is mass-used as a component of synthetic detergent to degrade proteins. Therefore a
文摘Desheptapeptide (B24 B30) insulin (DHPI), a virtually inactive insulin analog, has been crystallized in space group P2\-12\-12\-1 with two DHPI molecules in an asymmetric unit. The orientations and positions of the molecules were determined by molecular replacement, and a structural model was built at 0.3 nm resolution. The current model shows that the two DHPI monomers are related by a non crystallographic 2 fold axis, nearly parallel to the crystallographic c axis. This structural feature complicated the determination of the orientation of the local 2 fold axis, which was later confirmed by analysing the diffraction data of DHPI crystals.
基金Project supported by the National Natural Science Foundation of China (Grant Nos. 10674172 and 10874229)
文摘A previously published new rotation function has been improved by using a dynamic correlation coefficient as well as two new scoring functions of relative entropy and mean-square-residues to make the rotation function more robust and independent of a specific set of weights for scoring and ranking. The previously described new rotation function calculates the rotation function of molecular replacement by matching the search model directly with the Patterson vector map. The signal-to-noise ratio for the correct match was increased by averaging all the matching peaks. Several matching scores were employed to evaluate the goodness of matching. These matching scores were then combined into a single total score by optimizing a set of weights using the linear regression method. It was found that there exists an optimal set of weights that can be applied to the global rotation search and the correct solution can be ranked in the top 100 or less. However, this set of optimal weights in general is dependent on the search models and the crystal structures with different space groups and cell parameters. In this work, we try to solve this problem by designing a dynamic correlation coefficient. It is shown that the dynamic correlation coefficient works for a variety of space groups and cell parameters in the global search of rotation function. We also introduce two new matching scores： relative entropy and mean-square-residues. Last but not least, we discussed a valid method for the optimization of the adjustable parameters for matching vectors.
文摘From the conventional knowledge of protein nutrition to the molecular nutrition of amino acids, our understanding of protein/amino acid nutrition is rapidly increasing. Amino acids control cell growth and metabolism through two amino acid-sensingpathways, i.e. target of rapamycin complex 1 (TORC1) and the general control nonderepressible 2 (GCN2) signaling pathway.In the amino acid-abundant status, TORC1 dominates intracellular signaling and increases protein synthesis and cell growth.In contrast, amino acid deprivation actives GCN2 resulting in repression of general protein synthesis but facilitates the aminoacid transport and synthesis process. By integrating and coordinating nutrition and hormone signaling, TORC1 and GCN2control the switch of the catabolism and anabolism phase in most eukaryotes. Now, we appreciate that the availability ofindividual amino acids is sensed by intracellular sensors. These cutting-edge findings expand our knowledge of amino acidnutrition. Although the TORC1 and GCN2 were discovered decades ago, the study of molecular amino acid nutrition inaquaculture animals is still at its infancy. The aquaculture industry is highly dependent on the supply of fishmeal, which isthe major protein source in aquacultural animal diets. Some concerted efforts were conducted to substitute for fishmeal dueto limited supply of it. However, the concomitant issues including the unbalanced amino acid profile of alternative proteinsources limited the utilization of those proteins. Continued study of the molecular nutrition of amino acid in aquacultureanimals may be expected in the immediate future to expand our knowledge on the utilization of alternative protein sources.
文摘目的比较利伐沙班片和低分子肝素钙注射液预防老年关节置换术后下肢深静脉血栓的临床疗效。方法选取2015年2月—2016年5月天津港口医院收治的关节置换术患者120例为研究对象,所有患者根据用药方案不同分为低分子肝素组(64例)和利伐沙班组(56例)。低分子肝素组术后皮下注射低分子肝素钙注射液,0.2 m L/次,1次/d,第3天后剂量调整为0.4 m L/d。利伐沙班组术后口服利伐沙班片,10 mg/次,1次/d。两组患者连续治疗10 d。比较观察两组的深静脉血栓发生率、术中失血量、血液相关指标和血栓弹力图(TEG)。结果治疗后,两组深静脉血栓发生率比较差异无统计学意义。在关节置换手术中,两组术中总失血量和显性失血量比较差异无统计学意义。术后2、4 d,两组血红蛋白、血小板计数、PT和APTT比较差异无统计学意义。术后2、4 d,利伐沙班组D-二聚体(D-D)和纤维蛋白降解产物(FDP)显著低于低分子肝素组,国际标准化比值(INR)显著高于低分子肝素组,两组比较差异具有统计学意义(P<0.05)。术后2 d,利伐沙班组凝血因子反应时间(R)、血凝块成形时间(K)显著高于低分子肝素组,描记图最大曲线弧度作切线与水平线的夹角(Angle)、最大振幅(MA)和综合凝血指数(CI)显著低于低分子肝素组,两组比较差异具有统计学意义(P<0.05)。在治疗期间,低分子肝素组和利伐沙班组不良反应总发生率分别为46.88%、37.50%,两组比较差异具有统计学意义(P<0.05)。结论利伐沙班片预防老年关节置换术后下肢深静脉血栓优于低分子肝素钙注射液,可降低血液高凝状态,安全性较好,具有一定的临床推广应用价值。
