7CGD
Silver-bound E.coli malate dehydrogenase
Summary for 7CGD
| Entry DOI | 10.2210/pdb7cgd/pdb |
| Descriptor | Malate dehydrogenase, SILVER ION (3 entities in total) |
| Functional Keywords | malate dehydrogenase, silver, tca cycle, metal binding protein |
| Biological source | Escherichia coli K-12 |
| Total number of polymer chains | 4 |
| Total formula weight | 132381.20 |
| Authors | |
| Primary citation | Wang, H.,Yang, X.,Wang, M.,Hu, M.,Xu, X.,Yan, A.,Hao, Q.,Li, H.,Sun, H. Atomic differentiation of silver binding preference in protein targets: Escherichia coli malate dehydrogenase as a paradigm. Chem Sci, 11:11714-11719, 2020 Cited by PubMed Abstract: Understanding how metallodrugs interact with their protein targets is of vital importance for uncovering their molecular mode of actions as well as overall pharmacological/toxicological profiles, which in turn facilitates the development of novel metallodrugs. Silver has been used as an antimicrobial agent since antiquity, yet there is limited knowledge about silver-binding proteins. Given the multiple dispersed cysteine residues and histidine-methionine pairs, malate dehydrogenase (MDH) represents an excellent model to investigate silver coordination chemistry as well as its targeting sites in enzymes. We show by systematic biochemical characterizations that silver ions (Ag) bind MDH at multiple sites including three cysteine-containing sites. By X-ray crystallography, we unravel the binding preference of Ag to multiple binding sites in MDH, Cys113 > Cys251 > Cys109 > Met227. Silver exhibits preferences to the donor atoms and residues in the order of S > N > O and Cys > Met > His > Lys > Val, respectively, in MDH. For the first time, we report the coordination of silver to a lysine in proteins. Besides, we also observed argentophilic interactions (Ag⋯Ag, 2.7 to 3.3 Å) between two silver ions coordinating to one thiolate. Combined with site-directed mutagenesis and an enzymatic activity test, we unveil that the binding of Ag to the site IV (His177-Ag-Met227 site) plays a vital role in Ag-mediated MDH inactivation. This work stands as the first unusual and explicit study of silver binding preference to multiple binding sites in its authentic protein target at the atomic resolution. These findings enrich our knowledge on the biocoordination chemistry of silver(i), which in turn facilitates the prediction of the unknown silver-binding proteins and extends the pharmaceutical potentials of metal-based drugs. PubMed: 34123202DOI: 10.1039/d0sc04151c PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.06 Å) |
Structure validation
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