5UZQ
Crystal structure of citrate synthase from homo sapiens
Summary for 5UZQ
| Entry DOI | 10.2210/pdb5uzq/pdb |
| Descriptor | Citrate synthase (2 entities in total) |
| Functional Keywords | transferase |
| Biological source | Homo sapiens (Human) |
| Total number of polymer chains | 1 |
| Total formula weight | 51889.09 |
| Authors | Schlachter, C.,Chruszcz, M. (deposition date: 2017-02-27, release date: 2018-03-07, Last modification date: 2024-11-20) |
| Primary citation | Schlachter, C.R.,Klapper, V.,Radford, T.,Chruszcz, M. Comparative studies of Aspergillus fumigatus 2-methylcitrate synthase and human citrate synthase. Biol.Chem., 400:1567-1581, 2019 Cited by PubMed Abstract: Aspergillus fumigatus is a ubiquitous fungus that is not only a problem in agriculture, but also in healthcare. Aspergillus fumigatus drug resistance is becoming more prominent which is mainly attributed to the widespread use of fungicides in agriculture. The fungi-specific 2-methylcitrate cycle is responsible for detoxifying propionyl-CoA, a toxic metabolite produced as the fungus breaks down proteins and amino acids. The enzyme responsible for this detoxification is 2-methylcitrate synthase (mcsA) and is a potential candidate for the design of new anti-fungals. However, mcsA is very similar in structure to human citrate synthase (hCS) and catalyzes the same reaction. Therefore, both enzymes were studied in parallel to provide foundations for design of mcsA-specific inhibitors. The first crystal structures of citrate synthase from humans and 2-methylcitrate synthase from A. fumigatus are reported. The determined structures capture various conformational states of the enzymes and several inhibitors were identified and characterized. Despite a significant homology, mcsA and hCS display pronounced differences in substrate specificity and cooperativity. Considering that the active sites of the enzymes are almost identical, the differences in reactions catalyzed by enzymes are caused by residues that are in the vicinity of the active site and influence conformational changes of the enzymes. PubMed: 31141475DOI: 10.1515/hsz-2019-0106 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.16 Å) |
Structure validation
Download full validation report
