Fenna R, Zeng J, Davey C
Department of Biochemistry and Molecular Biology, University of Miami, Florida 33101.
Arch Biochem Biophys. 1995 Jan 10;316(1):653-6. doi: 10.1006/abbi.1995.1086.
A 3-A-resolution X-ray crystal structure of canine myeloperoxidase has previously revealed the overall structure of the molecule, including the polypeptide backbone conformation, but did not provide an unambiguous structure for the covalently bound heme. A higher resolution (2.28 A) X-ray crystal structure of human myeloperoxidase has now shown that the heme is a novel derivative of protoporphyrin IX in which three ring substituents form covalent bonds with amino acid side chains in the protein. Modified methyl groups on pyrrole rings A and C form ester linkages with glutamate 242 and aspartate 94, while a covalent bond between the vinyl group on ring A and the sulfur atom of methionine 243 results in a sulfonium ion linkage. The heme tetrapyrrole ring also shows considerable distortion from the planar conformation seen in most heme-containing proteins. The observed bending appears to result from these covalent bonds between diametrically opposed pyrrole rings A and C and the protein. Sequence comparisons suggest that the two ester linkages to the heme may also occur in other homologous mammalian peroxidases, but that the sulfonium ion linkage may be a unique feature of myeloperoxidase.
犬髓过氧化物酶的3埃分辨率X射线晶体结构先前已揭示了该分子的整体结构，包括多肽主链构象，但未提供共价结合血红素的明确结构。现在，人髓过氧化物酶的更高分辨率（2.28埃）X射线晶体结构表明，血红素是原卟啉IX的一种新型衍生物，其中三个环取代基与蛋白质中的氨基酸侧链形成共价键。吡咯环A和C上的修饰甲基与谷氨酸242和天冬氨酸94形成酯键，而环A上的乙烯基与甲硫氨酸243的硫原子之间的共价键形成锍离子键。血红素四吡咯环也显示出与大多数含血红素蛋白质中所见的平面构象有相当大的扭曲。观察到的弯曲似乎是由直径相对的吡咯环A和C与蛋白质之间的这些共价键引起的。序列比较表明，与血红素的两个酯键也可能出现在其他同源哺乳动物过氧化物酶中，但锍离子键可能是髓过氧化物酶的独特特征。
