Acta Crystallographica Section F最新文献

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Ternary structure of Plasmodium vivaxN-myristoyltransferase with myristoyl-CoA and inhibitor IMP-0001173. 疟原虫 N-肉豆蔻酰转移酶与肉豆蔻酰-CoA 和抑制剂 IMP-0001173 的三元结构。
Acta Crystallographica Section F Pub Date : 2024-10-01 DOI: 10.1107/s2053230x24008604
Cydni Bolling,Alex Mendez,Shane Taylor,Stanley Makumire,Alexandra Reers,Rachael Zigweid,Sandhya Subramanian,David M Dranow,Bart Staker,Thomas E Edwards,Edward W Tate,Andrew S Bell,Peter J Myler,Oluwatoyin A Asojo,Graham Chakafana
{"title":"Ternary structure of Plasmodium vivaxN-myristoyltransferase with myristoyl-CoA and inhibitor IMP-0001173.","authors":"Cydni Bolling,Alex Mendez,Shane Taylor,Stanley Makumire,Alexandra Reers,Rachael Zigweid,Sandhya Subramanian,David M Dranow,Bart Staker,Thomas E Edwards,Edward W Tate,Andrew S Bell,Peter J Myler,Oluwatoyin A Asojo,Graham Chakafana","doi":"10.1107/s2053230x24008604","DOIUrl":"https://doi.org/10.1107/s2053230x24008604","url":null,"abstract":"Plasmodium vivax is a major cause of malaria, which poses an increased health burden on approximately one third of the world's population due to climate change. Primaquine, the preferred treatment for P. vivax malaria, is contraindicated in individuals with glucose-6-phosphate dehydrogenase (G6PD) deficiency, a common genetic cause of hemolytic anemia, that affects ∼2.5% of the world's population and ∼8% of the population in areas of the world where P. vivax malaria is endemic. The Seattle Structural Genomics Center for Infectious Disease (SSGCID) conducted a structure-function analysis of P. vivax N-myristoyltransferase (PvNMT) as part of efforts to develop alternative malaria drugs. PvNMT catalyzes the attachment of myristate to the N-terminal glycine of many proteins, and this critical post-translational modification is required for the survival of P. vivax. The first step is the formation of a PvNMT-myristoyl-CoA binary complex that can bind to peptides. Understanding how inhibitors prevent protein binding will facilitate the development of PvNMT as a viable drug target. NMTs are secreted in all life stages of malarial parasites, making them attractive targets, unlike current antimalarials that are only effective during the plasmodial erythrocytic stages. The 2.3 Å resolution crystal structure of the ternary complex of PvNMT with myristoyl-CoA and a novel inhibitor is reported. One asymmetric unit contains two monomers. The structure reveals notable differences between the PvNMT and human enzymes and similarities to other plasmodial NMTs that can be exploited to develop new antimalarials.","PeriodicalId":501894,"journal":{"name":"Acta Crystallographica Section F","volume":"75 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142254476","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Crystal structure of guanosine 5'-monophosphate synthetase from the thermophilic bacterium Thermus thermophilus HB8. 嗜热菌 HB8 的鸟苷酸合成酶晶体结构。
Acta Crystallographica Section F Pub Date : 2024-10-01 DOI: 10.1107/s2053230x2400877x
Naoki Nemoto,Seiki Baba,Gota Kawai,Gen Ichi Sampei
{"title":"Crystal structure of guanosine 5'-monophosphate synthetase from the thermophilic bacterium Thermus thermophilus HB8.","authors":"Naoki Nemoto,Seiki Baba,Gota Kawai,Gen Ichi Sampei","doi":"10.1107/s2053230x2400877x","DOIUrl":"https://doi.org/10.1107/s2053230x2400877x","url":null,"abstract":"Guanosine 5'-monophosphate (GMP) synthetase (GuaA) catalyzes the last step of GMP synthesis in the purine nucleotide biosynthetic pathway. This enzyme catalyzes a reaction in which xanthine 5'-monophosphate (XMP) is converted to GMP in the presence of Gln and ATP through an adenyl-XMP intermediate. A structure of an XMP-bound form of GuaA from the domain Bacteria has not yet been determined. In this study, the crystal structure of an XMP-bound form of GuaA from the thermophilic bacterium Thermus thermophilus HB8 (TtGuaA) was determined at a resolution of 2.20 Å and that of an apo form of TtGuaA was determined at 2.10 Å resolution. TtGuaA forms a homodimer, and the monomer is composed of three domains, which is a typical structure for GuaA. Disordered regions in the crystal structure were obtained from the AlphaFold2-predicted model structure, and a model with substrates (Gln, XMP and ATP) was constructed for molecular-dynamics (MD) simulations. The structural fluctuations of the TtGuaA dimer as well as the interactions between the active-site residues were analyzed by MD simulations.","PeriodicalId":501894,"journal":{"name":"Acta Crystallographica Section F","volume":"5 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142254475","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Glucose-6-phosphate dehydrogenase and its 3D structures from crystallography and electron cryo-microscopy. 葡萄糖-6-磷酸脱氢酶及其晶体学和电子冷冻显微镜三维结构。
Acta Crystallographica Section F Pub Date : 2024-10-01 DOI: 10.1107/s2053230x24008112
Stefania Hanau,John R Helliwell
{"title":"Glucose-6-phosphate dehydrogenase and its 3D structures from crystallography and electron cryo-microscopy.","authors":"Stefania Hanau,John R Helliwell","doi":"10.1107/s2053230x24008112","DOIUrl":"https://doi.org/10.1107/s2053230x24008112","url":null,"abstract":"Glucose-6-phosphate dehydrogenase (G6PD) is the first enzyme in the pentose phosphate pathway. It has been extensively studied by biochemical and structural techniques. 13 X-ray crystal structures and five electron cryo-microscopy structures in the PDB are focused on in this topical review. Two F420-dependent glucose-6-phosphate dehydrogenase (FGD) structures are also reported. The significant differences between human and parasite G6PDs can be exploited to find selective drugs against infections such as malaria and leishmaniasis. Furthermore, G6PD is a prognostic marker in several cancer types and is also considered to be a tumour target. On the other hand, FGD is considered to be a target against Mycobacterium tuberculosis and possesses a high biotechnological potential in biocatalysis and bioremediation.","PeriodicalId":501894,"journal":{"name":"Acta Crystallographica Section F","volume":"410 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142214049","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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