细菌血红素降解蛋白结构特点及作用机制

铁离子是几乎所有生物包括细菌生存必需的营养元素. 在宿主体内，绝大多数的铁离子均以血红素的形式存在于各种血红素结合蛋白，如血红蛋白、肌红蛋白等. 当致病菌感染宿主后，血红素将成为某些致病菌主要的铁离子来源. 致病菌编码血红素转运系统，并利用该系统将血红素转运至胞浆，在胞浆血红素被细菌的血红素降解蛋白降解，释放铁离子供细菌利用. 在致病菌中,目前至少有两种血红素降解酶被发现和鉴定. 第一种为经典的血红素氧化酶(heme oxygenase, HO)，它催化血红素氧化形成胆绿素、一氧化碳(CO)和Fe2+;第二种非经典降解酶,包括金黄色葡萄球菌的IsdG/IsdI蛋白及其同系物MhuD蛋白，催化血红素分别产生staphylobilin和mycobilin. 另外，部分细菌内存在其它血红素降解因子，其与前两种血红素降解酶无结构同源性，但在血红素降解实验中可产生胆绿素(biliverdin)或CO，因而被鉴定为“血红素降解蛋白”. 对细菌血红素降解蛋白分子结构解析及作用机制的深入理解，将有助于新的血红素降解蛋白的发现和鉴定.

Structural Properties and Molecular Mechanisms of Heme-degrading Proteins in Bacteria

Iron is an essential nutrient for almost all organisms, including bacteria. In the host, the most parts of iron exist in the form of heme which is bound by heme-containing proteins such as hemeoglobin, myoglobin. For some pathogenic bacteria, heme of host can be a main iron source.Pathogenic bacteria encode for the heme acquisition system that is able to transport heme into cytoplasm. In cytoplasm, heme must be degraded to release iron. To date, main two kinds of heme-degrading proteins were found and identified in bacteria. The canonical heme-degrading proteins, heme oxygenases (HOs), catalyze the oxidation of heme to biliverdin, CO, and ferrous iron. Another kind of noncanonical heme-degrading proteins includes IsdI/IsdG of S. aureus and the homologous MhuD of M. tuberculosis. The IsdI/IsdG and MhuD convert heme to staphylobilin and mycobilin, respectively. In addition, it has recently been reported that several bacteria exist “heme-degrading factors”, which have no structural homology with characterized heme-degrading proteins. Many of these proteins degrade heme to produce biliverdin or CO. To understand the molecular mechanisms of heme degradation in bacteria will contribute to find and identify novel heme-degrading proteins.