The full-length structure of "Red Magusase" is finally cracked.

P450 enzyme contains hemoglobin and can catalyze various different reactions such as hydroxy, cyclic oxidation, dealkylation, carbon-carbon coupling, oxidizing, etc., so it is called "red universal enzyme", through enzyme catalysis can solve the environmental pollution problemcause of drug and chemical production processBut since the discovery of P450 enzymes for decades, its crystal structure has not been resolved, and the catalytic mechanism has puzzled the scientific communityrecently, Professor Chen Chunqi of Hubei University's School of Life Sciences and the Ministry of The National Key Laboratory of Biocatalytic and Enzyme Engineering, in cooperation with Professor Ma Lixin and Professor Guo Ruiting, successfully solved the difficult problem and made an important breakthrough in the research mechanism of the complete catalytic mechanism of P450 enzyme: clarifying how electrons enter the reaction mechanism of the substrate binding area from the reductase regionThe findings are published in the latest issue of Nature Communicationseasily fracture-degraded and degraded, it is difficult to see the true face of P450 enzymes
"There are many different kinds of P450 enzymes in nature, they are involved in the physiological regulation of cells, drug metabolism, and the synthesis of many important drugsChen Chunqi introduced, for example, we human chromosomes have more than 50 P450 enzyme genes, they are responsible for cholesterol, sterol hormones and vitamin D and other important compounds synthesis;scientists have found that P450 enzymes can identify a variety of substrates (substances involved in biochemical reactions), thus genetically engineering The Use of P450 enzymes to tailor chemical reactions, making it a hot topic of researchProfessor Arnold, winner of the 2018 Nobel Prize in Chemistry, won the prize for transforming the P450 enzyme for a variety of special chemical reactionsa complete P450 enzyme system consists of three components: a substrate binding region with hemoglobin; "It's like an electrical appliance that needs to be plugged in to work, and the substrate binding area with hemoglobin is like the appliance itself, the outlet is like a reductase, and the wire is the electronic channel connecting the ends." Chen explained that when building a P450 enzyme reaction system, all the components need to be found together and assembled to be able to react to a catalytic reactionThere are three components are connected to the P450 enzyme, called the "self-sufficient P450 enzyme", such a system does not need to find a matching "power supply" and "wire", so in the application has a huge advantage, is also convenient for scientists to study the "star" P450 enzymeThe research on the mechanism of hemoglobin binding of P450 enzyme has been quite mature, and there are many studies on the transformation of the substrate binding area, but there are still many unknowns about how electrons are fed from reductase to the active centerThis requires the acquisition of the crystal structure of the P450 enzyme, i.ethe full appearance of the enzymeBecause the full length P450 enzyme in the expression, purification, the enzyme protein is easy to break, degrade off, so it is difficult to obtain its complete crystal, the structure of the identification of full-length P450 enzyme has not been any breakthrough"look" at the full-length structure, unlock the P450 enzyme catalytic path
Chen Chunqi led the structural biology research team through unremitting efforts to find a source from the heat-resistant bacteria in the "self-sufficient" P450 enzyme, this P450 enzyme at a high temperature of 70 degrees C is also particularly stable, will not break or degrade, so it is particularly easy to crystallize Using advanced X-ray crystallography technology, Chen's team successfully analyzed the high-resolution full-length structure of the self-sufficient P450 enzyme " We have found that the entire P450 enzyme's three components, from the sequence of genes in order: hemoglobin binding region - reductase domain - ferrite also protein domain Each of the three regions has a cofactor, three of which become a transit point for the internal electronic transmission of P450 enzymes Electronic delivery is like delivery, it requires several transit stations Chen Chunqi introduced, the crystal structure shows that hemoglobin binding region and reductase are located at both ends of the entire protein, hemoglobin binding region at this end facing outwards, exposing the opening to facilitate the entry of the substrate, and electronic transmission through several transit stations, and finally successfully delivered to hemoglobin for catalytic reaction researchers observed a large number of amino acids in the middle and confirmed that several of them were important for the electronic transmission of P450 enzymes This is the first time at home and abroad to analyze the "self-sufficient P450 enzyme" full-length three-dimensional structure, is a very important milestone, for other types of P450 enzyme transformation and application has an important guiding significance Chen Chunqi said that their research team is currently using the obtained structural information to accelerate the P450 enzyme for more in-depth design and transformation, with a view to the development of new enzymes that can catalyze more important reactions, the early realization of P450 enzyme green biological process manufacturing, and applied to the biotechnology, pharmaceutical engineering and chemical industry (
Bio valley Bioon.com)