Microbiology Department, The University of Georgia, Athens, GA, USA.
J Bacteriol. 2013 Sep;195(18):4154-60. doi: 10.1128/JB.00587-13. Epub 2013 Jul 12.
Early studies of Helicobacter pylori's nutritional requirements alluded to a complete purine salvage network in this organism. Recently, this hypothesis was confirmed in two strains of H. pylori, whose purine requirements were satisfied by any single purine base or nucleoside. Most of the purine conversion enzymes in H. pylori have been studied using mutant analysis; however, the gene encoding adenosine deaminase (ADD) in H. pylori remained unidentified. Through stepwise protein purification followed by matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF), we discovered that H. pylori ADD is encoded by hp0267, an apparently essential gene. Hp0267 shares no sequence homology with previously characterized ADDs, yet both are members of the amidohydrolase superfamily. Hp0267 is grouped within cog0402, while other ADDs studied to date are found in cog1816. The hp0267 locus was previously misannotated as encoding a chlorohydrolase. Using purified recombinant Hp0267, we determined the enzyme's pH optimum, temperature optimum, substrate specificity, and estimated kinetic constants. In contrast to other known ADDs, Hp0267 contains Fe(II) as the relevant metal ligand. Furthermore, Hp0267 exhibits very low deaminase activity on 2'-deoxyadenosine, a substrate that is readily hydrolyzed by cog1816 ADDs. Our preliminary comparative genomic analysis suggests that Hp0267 represents a second enzyme class of adenosine deaminase whose phyletic distribution among prokaryotes is broad.
早期对幽门螺杆菌营养需求的研究暗示该生物体内存在完整的嘌呤回收网络。最近,这一假说在两种幽门螺杆菌菌株中得到了证实,这两种菌株的嘌呤需求可以通过任何单一的嘌呤碱基或核苷来满足。幽门螺杆菌中大多数嘌呤转化酶已通过突变分析进行了研究;然而,幽门螺杆菌中腺苷脱氨酶(ADD)的编码基因仍然未知。通过逐步的蛋白质纯化,然后进行基质辅助激光解吸电离飞行时间质谱(MALDI-TOF)分析,我们发现幽门螺杆菌的 ADD 由 hp0267 编码,这是一个明显的必需基因。Hp0267 与先前表征的 ADD 没有序列同源性,但它们都是酰胺水解酶超家族的成员。Hp0267 被归类为 cog0402 内,而迄今为止研究过的其他 ADD 则存在于 cog1816 中。Hp0267 基因座之前被错误注释为编码氯水解酶。使用纯化的重组 Hp0267,我们确定了酶的 pH 最佳值、温度最佳值、底物特异性,并估算了动力学常数。与其他已知的 ADD 不同,Hp0267 含有 Fe(II)作为相关的金属配体。此外,Hp0267 对 2'-脱氧腺苷的脱氨酶活性非常低,而 cog1816 ADD 很容易水解 2'-脱氧腺苷。我们初步的比较基因组分析表明,Hp0267 代表了第二种腺苷脱氨酶酶类,其在原核生物中的系统发生分布非常广泛。