Karlberg Tobias, Lecerof David, Gora Monika, Silvegren Germund, Labbe-Bois Rosine, Hansson Mats, Al-Karadaghi Salam
Department of Molecular Biophysics, Centre for Chemistry and Chemical Engineering, Lund University, Sweden.
Biochemistry. 2002 Nov 19;41(46):13499-506. doi: 10.1021/bi0260785.
Ferrochelatase is the terminal enzyme in the heme biosynthetic pathway. It catalyzes the insertion of ferrous iron into protoporphyrin IX to produce protoheme IX. The crystal structures of ferrochelatase from Saccharomyces cerevisiae in free form, in complex with Co(II), a substrate metal ion, and in complex with two inhibitors, Cd(II) and Hg(I), are presented in this work. The enzyme is a homodimer, with clear asymmetry between the monomers with regard to the porphyrin binding cleft and the mode of metal binding. The Co(II) and Cd(II) complexes reveal the metal binding site which consists of the invariant amino acids H235, E314, and S275 and solvent molecules. The shortest distance to the metal reveals that amino acid H235 is the primary metal binding residue. A second site with bound Cd(II) was found close to the surface of the molecule, approximately 14 A from H235, with E97, H317, and E326 participating in metal coordination. It is suggested that this site corresponds to the magnesium binding site in Bacillus subtilis ferrochelatase. The latter site is also located at the surface of the molecule and thought to be involved in initial metal binding and regulation.
亚铁螯合酶是血红素生物合成途径中的末端酶。它催化亚铁离子插入原卟啉IX中以生成原血红素IX。本文展示了来自酿酒酵母的亚铁螯合酶的游离形式、与底物金属离子Co(II)形成的复合物以及与两种抑制剂Cd(II)和Hg(I)形成的复合物的晶体结构。该酶是一种同二聚体，在卟啉结合裂隙和金属结合模式方面，单体之间存在明显的不对称性。Co(II)和Cd(II)复合物揭示了由不变氨基酸H235、E314和S275以及溶剂分子组成的金属结合位点。到金属的最短距离表明氨基酸H235是主要的金属结合残基。在分子表面附近发现了一个结合有Cd(II)的第二个位点，距离H235约14 Å，E97、H317和E326参与金属配位。有人认为该位点对应于枯草芽孢杆菌亚铁螯合酶中的镁结合位点。后一个位点也位于分子表面，被认为参与初始金属结合和调节。
