32 results about "Protein crystal structure" patented technology

Disclosed is a crystal comprising at least a catalytically active portion of a SET 7 / 9 histone methyltransferase, and various uses thereof, and ligands for SET 7 / 9.

The invention discloses a sorghum C2H2 zinc finger protein gene SbZFP36. The nucleotide sequence of the sorghum C2H2 zinc finger protein gene SbZFP36 is shown as SEQ ID NO. 1. The invention also discloses a protein encoded by the sorghum C2H2 zinc finger protein gene SbZFP36, and the amino acid sequence of the protein is shown as SEQ ID NO. 2. The invention also discloses a recombinant vector containing the sorghum C2H2 zinc finger protein gene SbZFP36 and an expression method. According to the invention, a sorghum homologous gene SbZFP36 is obtained from a sorghum genome database through theprotein sequence of a rice ZFP gene, the full length of the gene is 711bp, a prokaryotic expression vector is constructed according to the gene, a protein purification system is used for purifying theprokaryotic expression vector, the result lays a foundation for further researching the protein crystal structure and biological characteristics, and a basis is further provided for improving the disease resistance of sorghum through a gene editing method.

The invention provides an islet-targeted protein and a eukaryotic expression method thereof. The method comprises the following steps of (1) constructing plasmids containing a protein coding gene IGRP206-214-dtSCT; (2) recombining the plasmids into a chromosome of saccharomyces pastorianus; and (3) obtaining a target protein through methanol fermentation induction. A soluble IGRP206-214MHC compound is prepared through an eukaryotic expression system. Compared with the previously prepared protein for prokaryotic expression, the islet-targeted protein has galactosylated modification, and is closer to an in-vivo protein crystal structure, and the recognition rate of specific CTL on the protein and the bonding stability of TCR and an MHC molecule are improved, the endocytosis amount of viruses coupled to the protein is increased, the efficacy of the recombinant protein is improved and the recombinant protein is more stable in an external environment after galactosylated modification, and the storage period is prolonged.

The invention provides a botulinum neurotoxin protein crystal structure and a crystal preparation method and determination method. The crystal has a space group P2<1>2<1>2<1>, and crystal cell parameters are as shown in the description. Through a genetic engineering method, BONT proteins being high in purity can be successfully expressed and purified, and besides, a crystallizing condition that the proteins can form perfect crystal forms can be screened; and finally, through X ray crystal diffraction, crystal data is collected, and the crystal structure of the proteins is further determined. Afoundation is provided for medicine design and an associated molecular action mechanism based on the protein structure in the future.

The invention belongs to the field of bio-medicine, and in particular relates to an application of a small-molecule covalent inhibitor in preparing a medicine for inhibiting S-adenosylmethionine decarboxylase and a screening method. The structural formula of the small-molecule covalent inhibitor is as shown in Description, wherein R1 represents phenyl or aniline or benzamide or a substituted phenyl group thereof, methyl or ethyl or furan and a substituted group thereof, pyrrole and a substituted group thereof, pyridine and a substituted group thereof and the like; and the inhibitor further consists of pharmaceutically acceptable salt with a chemical structure shown as general formula I. A method for screening the small-molecule covalent inhibitor of the S-adenosylmethionine decarboxylase comprises the following steps: deleting pyruvoyl 68 residue in an S-adenosylmethionine decarboxylase crystal structure, and conducting optimizing in Rosetta software so as to obtain an optimized protein crystal structure; and conducting docking calculation on the optimized protein crystal structure and a searched small-molecule structure by virtue of AutoDockVina software, and screening calculating results in accordance with a grading order so as to obtain the small-molecule covalent inhibitor.

The invention belongs to the field of bio-medicine, and in particular relates to an application of a small-molecule covalent inhibitor in preparing a medicine for inhibiting S-adenosylmethionine decarboxylase and a screening method of the small-molecule covalent inhibitor. The structural formula of the small-molecule covalent inhibitor is as shown in Description, wherein R1 represents formyl and a derivative substituted group thereof, amino and a derivative substituted group thereof or thienyl, and R2 in an R2 group represents cyclohexene and a substituted group thereof, phenyl and a substituted group thereof, aniline or benzamide or a substituted phenyl group thereof, pyrrole and a substituted group thereof, or pyridine and a substituted group thereof; and the inhibitor further consists of pharmaceutically acceptable salt with a chemical structure shown as general formula I. A method for screening the small-molecule covalent inhibitor of the S-adenosylmethionine decarboxylase comprises the following steps: deleting pyruvoyl 68 residue in an S-adenosylmethionine decarboxylase crystal structure, and conducting optimizing in Rosetta software so as to obtain an optimized protein crystal structure; and conducting docking calculation on the optimized protein crystal structure and a searched small-molecule structure by virtue of AutoDockVina software, and screening calculating results so as to obtain the small-molecule covalent inhibitor.

The invention provides a high-viscosity extrusion jet sample loading device for protein crystal structure analysis. The high-viscosity extrusion jet sample loading device comprises: a liquid inlet section connected with a hydraulic device; a piston section which is connected with the liquid inlet section and comprises a piston rod which reciprocates in the piston section; a sample section connected to the piston section, wherein the one end of the piston rod is in contact with liquid input by the liquid inlet section, and the other end of the piston rod is in contact with a viscous sample in the sample section; an air inlet section which is connected with the sample section through a capillary tube; an intersection section which is connected with the gas inlet section, wherein gas from the gas inlet section focuses the viscous sample extruded from the capillary tube into stable jet flow through shear force, and the stable jet flow is kept at the intersection section to interact with the X-ray; a recovery section which is connected with the intersection section; a fixed section which is connected with the intersection section; and an off-line separation section insertable between the sample section and the intake section. The device not only can be used for collecting crystal serial data, but also can be used for time resolution experiments of protein crystals, and has a good application prospect in the field of protein crystal structure analysis.

The invention relates to a method for screening hepatotoxic compounds in polygonum multiflorum based on a computer molecular docking technology. The method comprises the following steps: (1) obtaining a three-dimensional chemical structure of at least one compound to be detected in the polygonum multiflorum; (2) obtaining a protein crystal structure of the farnesoid X receptor, and determining an active site of the farnesoid X receptor; (3) respectively carrying out computer molecular docking on the compound to be detected and a positive compound with a farnesoid X receptor inhibition effect and the active sites to obtain docking scores; and (4) judging the to-be-detected compound as the hepatotoxic compound under the condition that the docking score of the to-be-detected compound reaches a docking judgment value. The screening method disclosed by the invention is rapid, economical and simple to operate, and can realize high-throughput screening of numerous compounds.

The invention belongs to the field of bio-medicine, and in particular relates to an application of a small-molecule covalent inhibitor in preparing a medicine for inhibiting S-adenosylmethionine decarboxylase and a screening method of the small-molecule covalent inhibitor. The structural formula of the small-molecule covalent inhibitor is as shown in Description, wherein R1 represents phenyl or aniline or benzamide or an alkyl group or furan or pyrrole or pyridine and a substituted group thereof. A method for screening the small-molecule covalent inhibitor of the S-adenosylmethionine decarboxylase comprises the following steps: deleting pyruvoyl 68 residue in an S-adenosylmethionine decarboxylase crystal structure, and conducting optimizing in Rosetta software so as to obtain an optimized protein crystal structure; and conducting docking calculation on the optimized protein crystal structure and a searched small-molecule structure by virtue of AutoDockVina software, and screening calculating results in accordance with a grading order so as to obtain the small-molecule covalent inhibitor.

The invention belongs to the field of bio-medicine, and in particular relates to an application of a small-molecule covalent inhibitor in preparing a medicine for inhibiting S-adenosylmethionine decarboxylase and a screening method of the small-molecule covalent inhibitor. The structural formula of the small-molecule covalent inhibitor is as shown in Description, wherein R1 represents phenyl or aniline or benzamide or an alkyl group or furan or pyrrole or pyridine and a substituted group thereof. A method for screening the small-molecule covalent inhibitor of the S-adenosylmethionine decarboxylase comprises the following steps: deleting pyruvoyl 68 residue in an S-adenosylmethionine decarboxylase crystal structure, and conducting optimizing in Rosetta software so as to obtain an optimized protein crystal structure; and conducting docking calculation on the optimized protein crystal structure and a searched small-molecule structure by virtue of AutoDockVina software, and screening calculating results in accordance with a grading order so as to obtain the small-molecule covalent inhibitor.

The invention provides the application of a group of active compounds in the preparation of drugs for inhibiting DJ-1 dimerization. A group of 23 compounds that inhibit DJ-1 dimerization were discovered through computer-aided virtual methods and techniques based on DJ-1 protein crystal structure, medicinal chemistry knowledge, and pharmacological activity screening. According to the compounds whose structural similarity coefficient Tanimoto value is greater than 0.85, have similar biological activity principles, it is determined that the molecular structural similarity Tanimoto value of this group of compounds is greater than 0.85, and also have similar inhibitory DJ-1 activity. The invention takes the DJ-1 protein related to the occurrence and development of tumor as the research object, and screens to obtain the compound capable of inhibiting the dimerization of the DJ-1 protein and inhibiting the proliferation of tumor cells. These compounds can not only inhibit the dimerization of DJ-1 protein, but also have strong inhibitory activity on tumor cells, and have good prospects for drug development.

This invention provides one effective and rapid method to extract target molecule and target compound find three dimensional structure from Chinese medicine product, which uses target protein transistor stricture as base and uses X ray transistor means to filter the product for active component and for study from one new respective.

Based on the protein crystal structure of human vascular endothelial growth factor receptor-3 (VEGFR-3), the present invention designs and develops a polypeptide that specifically binds to it, and discloses its screening method, identification and use. The general formula of the amino acid sequence of the polypeptide is CXXPFXP, X is any L-type or D-type amino acid in 20 kinds of natural amino acids. The present invention also relates to the amide, ester or salt of the polypeptide, or the active fragment, active derivative and fusion polypeptide formed by the polypeptide, or the polymer formed by using the polypeptide as a ligand. Using computer simulation screening and immunofluorescence in vitro verification to obtain tumor-targeting polypeptides with high expression of VEGFR-3, it is convenient and quick. The screened polypeptides have clear structures, high affinity with target proteins, almost no immunogenicity, and are easy to prepare and produce. It has broad application prospects in the fields of tumor-targeted drug delivery, imaging and diagnosis, and gene transfection.

The invention discloses a construction and prediction method of an integrated drug target prediction system. The method comprises the following steps of: analyzing a protein crystal structure database; selecting the protein bound with the drug-like ligand small molecule or the protein with the small molecule ligand binding potential as a target point, and building a crystal structure database of targets; for these targets, collecting the information of the targets related to diseases, the biology type and the active small molecule ligand information, and integrating a comprehensive target screening database composed of an active site database, a pharmacophore database, a small molecular compound database and a target basic information database. Based on the comprehensive target screening database, the construction of the integrated drug target prediction system is realized through a script program or a PipelinePilot flow, and the probability of target prediction accuracy of the method is provided. The method provided by the invention exerts the three above technical advantages to provide the probability of target prediction, thereby providing effective basis for further experimental verification.