1ACO

CRYSTAL STRUCTURE OF ACONITASE WITH TRANSACONITATE BOUND

1ACO の概要

• エントリーDOI: 10.2210/pdb1aco/pdb
• 分子名称: ACONITASE, ACONITATE ION, IRON/SULFUR CLUSTER, ... (4 entities in total)
• 機能のキーワード: lyase(carbon-oxygen)
• 由来する生物種: Bos taurus (cattle)
• 細胞内の位置: Mitochondrion : P20004
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 83270.63

構造登録者

Stout, C.D. (登録日: 1993-01-17, 公開日: 1993-10-31, 最終更新日: 2024-10-30)

主引用文献

Lauble, H.,Kennedy, M.C.,Beinert, H.,Stout, C.D.
Crystal structures of aconitase with trans-aconitate and nitrocitrate bound.
J.Mol.Biol., 237:437-451, 1994

PubMed Abstract: Crystal structures of mitochondrial aconitase with the inhibitors trans-aconitate and nitrocitrate bound to the [4Fe-4S] cluster have been solved and refined at 2.05 A resolution with R-factors of 0.168 and 0.172, respectively. Crystallization of aconitase with the substrates citrate and cis-aconitate has not been possible because the enzyme turns over and selects enzyme with isocitrate bound into the crystal lattice. Therefore we have analyzed crystal structures of the enzyme complexed with inhibitor analogs of these two substrates. The structure with nitrocitrate bound provides a model for citrate binding. The structure with trans-aconitate bound provides a model for cis-aconitate binding in two ways: Fe4 of the [4Fe-4S] cluster is five-coordinate and the carbon at the C beta position is trigonal. These results allow the model for the reaction mechanism to be extended to all three natural substrates of aconitase. The results support a model in which citrate and isocitrate form similar chelate structures related by 180 degrees rotation about the C alpha-C beta bond while the intermediate cis-aconitate binds in either of two ways (citrate mode or isocitrate mode). In both inhibitor complexes a H2O molecule is also bound to Fe4. In the structure with nitrocitrate bound, partial occupancy of sulfate in the active site is observed accompanied by hydroxyl binding to Fe4. Comparison of the structures with isocitrate, trans-aconitate, nitrocitrate and sulfate bound reveals preferred orientations for the three types of oxygens ligated to Fe4 (carboxyl, hydroxyl and H2O) supporting the proposed roles for His101, Asp165 and His167 in the catalytic mechanism.

PubMed: 8151704
DOI: 10.1006/jmbi.1994.1246

実験手法

X-RAY DIFFRACTION (2.05 Å)