Bohle D Scott, Kosar Andrew D, Stephens Peter W
Department of Chemistry, University of Wyoming, Laramie, Wyoming, 82071-3838, USA.
Acta Crystallogr D Biol Crystallogr. 2002 Oct;58(Pt 10 Pt 1):1752-6. doi: 10.1107/s0907444902014294. Epub 2002 Sep 26.
Hemoglobin digestion in the intraerythrocytic trophozoite stages of the malaria parasite releases large quantities of heme, which is then detoxified by crystallization into regular crystallites, which are subsequently secreted into the host vascular network as malaria pigment. This crystalline product is isostructural with the synthetic phase b-hematin, and its structure, solved from its powder diffraction pattern, (Pagola et al., 2000), corresponds to a hydrogen bonded chain of propionate linked dimers, Figure 1. This is an example where the crystalline phase is the macromolecule of direct biological interest, particularly in light of the currently accepted hypothesis for the quinoline antimalarial drug action being the inhibition of b-hematin formation and biosynthesis. A surprisingly array of spectroscopically similar closely related phases can also form during the reactions which are used to synthesize b-hematin. Scanning electron microscopy and X-ray powder diffraction have been used to characterize these materials. Taken together these results indicate that infrared spectroscopy, in itself, is insufficient to identify synthetic analogs to malaria pigment and that a combination of electronmicroscopy and powder diffraction are required to unambiguously characterize these heme aggregates.
疟原虫红细胞内滋养体阶段的血红蛋白消化会释放大量血红素，随后血红素通过结晶形成规则的微晶进行解毒，这些微晶随后作为疟色素分泌到宿主血管网络中。这种结晶产物与合成的β-血红素同构，其结构由粉末衍射图谱解析得出（帕戈拉等人，2000年），对应于由丙酸盐连接的二聚体形成的氢键链，如图1所示。这是一个结晶相是具有直接生物学意义的大分子的例子，特别是鉴于目前被广泛接受的关于喹啉抗疟药物作用的假说，即抑制β-血红素的形成和生物合成。在用于合成β-血红素的反应过程中，还会形成一系列令人惊讶的光谱相似且密切相关的相。扫描电子显微镜和X射线粉末衍射已被用于表征这些材料。综合这些结果表明，仅靠红外光谱本身不足以鉴定疟色素的合成类似物，明确表征这些血红素聚集体需要电子显微镜和粉末衍射相结合。
