3GZC の概要
| エントリーDOI | 10.2210/pdb3gzc/pdb |
| 分子名称 | Selenocysteine lyase, (5-HYDROXY-4,6-DIMETHYLPYRIDIN-3-YL)METHYL DIHYDROGEN PHOSPHATE (3 entities in total) |
| 機能のキーワード | scly, selenocysteine, lyase, human, pyridoxal-5'-phosphate, plp, structural genomics, structural genomics consortium, sgc, pyridoxal phosphate, transferase |
| 由来する生物種 | Homo sapiens (Human) |
| 細胞内の位置 | Cytoplasm, cytosol (By similarity): Q96I15 |
| タンパク質・核酸の鎖数 | 2 |
| 化学式量合計 | 96042.68 |
| 構造登録者 | Collins, R.,Hogbom, M.,Arrowsmith, C.,Berglund, H.,Edwards, A.,Ehn, M.,Flodin, S.,Flores, A.,Graslund, S.,Hallberg, B.M.,Hammarstrom, M.,Karlberg, T.,Kotenyova, T.,Nilsson-Ehle, P.,Nordlund, P.,Nyman, T.,Ogg, D.,Persson, C.,Sagemark, J.,Stenmark, P.,Sundstrom, M.,Thorsell, A.G.,Uppenberg, J.,Van Den Berg, S.,Weigelt, J.,Holmberg-Schiavone, L.,Schuler, H.,Structural Genomics Consortium (SGC) (登録日: 2009-04-07, 公開日: 2009-04-28, 最終更新日: 2024-10-09) |
| 主引用文献 | Collins, R.,Johansson, A.L.,Karlberg, T.,Markova, N.,van den Berg, S.,Olesen, K.,Hammarstrom, M.,Flores, A.,Schuler, H.,Schiavone, L.H.,Brzezinski, P.,Arner, E.S.,Hogbom, M. Biochemical discrimination between selenium and sulfur 1: a single residue provides selenium specificity to human selenocysteine lyase. Plos One, 7:e30581-e30581, 2012 Cited by PubMed Abstract: Selenium and sulfur are two closely related basic elements utilized in nature for a vast array of biochemical reactions. While toxic at higher concentrations, selenium is an essential trace element incorporated into selenoproteins as selenocysteine (Sec), the selenium analogue of cysteine (Cys). Sec lyases (SCLs) and Cys desulfurases (CDs) catalyze the removal of selenium or sulfur from Sec or Cys and generally act on both substrates. In contrast, human SCL (hSCL) is specific for Sec although the only difference between Sec and Cys is the identity of a single atom. The chemical basis of this selenium-over-sulfur discrimination is not understood. Here we describe the X-ray crystal structure of hSCL and identify Asp146 as the key residue that provides the Sec specificity. A D146K variant resulted in loss of Sec specificity and appearance of CD activity. A dynamic active site segment also provides the structural prerequisites for direct product delivery of selenide produced by Sec cleavage, thus avoiding release of reactive selenide species into the cell. We thus here define a molecular determinant for enzymatic specificity discrimination between a single selenium versus sulfur atom, elements with very similar chemical properties. Our findings thus provide molecular insights into a key level of control in human selenium and selenoprotein turnover and metabolism. PubMed: 22295093DOI: 10.1371/journal.pone.0030581 主引用文献が同じPDBエントリー |
| 実験手法 | X-RAY DIFFRACTION (2.1 Å) |
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