Plasmodium falciparum hydroxymethylbilane synthase does not house any cosynthase activity within the haem biosynthetic pathway
Plasmodium falciparum hydroxymethylbilane synthase does not house any cosynthase activity within the haem biosynthetic pathway
复制标题
恶性疟原虫羟甲基乙烷合酶在血红素生物合成途径中不具有任何辅合酶活性
DOI：
10.1101/2021.02.09.429727
复制
发表时间：
2021
期刊：
影响因子：
--
通讯作者：
Scott A
中科院分区：
文献类型：
--
作者：
Scott A
尿卟啉原III是大环修饰四吡咯的通用前体，由氨基乙酰丙酸（ALA）通过涉及三种酶的保守途径产生：卟啉原合酶（PBGS）、羟甲基胆烷合酶（HmbS）和尿卟啉原III合酶（UroS）。编码尿卟啉原III合酶的基因尚未在恶性疟原虫中被鉴定，但已表明该活性被安置在双功能羟甲基胆烷合酶（HmbS）内。此外，由PF3D7_1247600编码的未知蛋白质也被预测具有UroS活性。在这项研究中，它表明，这两种蛋白质都不具有UroS活性和真实的UroS仍有待确定。密码子优化的基因不能补充UroS活性缺陷的确定的大肠杆菌hemD−突变体（SASZ 31）证明了这一点。此外，对重组、纯化的P. falciparumHmbS显示只能检测到尿卟啉I（对应于羟甲基胆烷的产生）。未检测到尿卟啉III，表明P.恶性疟原虫HmbS不具有UroS活性，仅能催化胆色素原形成羟甲基胆烷。
Uroporphyrinogen III, the universal progenitor of macrocyclic, modified tetrapyrroles, is produced from aminolaevulinic acid (ALA) by a conserved pathway involving three enzymes: porphobilinogen synthase (PBGS), hydroxymethylbilane synthase (HmbS) and uroporphyrinogen III synthase (UroS). The gene encoding uroporphyrinogen III synthase has not yet been identified inPlasmodium falciparum, but it has been suggested that this activity is housed inside a bifunctional hybroxymethylbilane synthase (HmbS). Additionally, an unknown protein encoded by PF3D7_1247600 has also been predicted to possess UroS activity. In this study it is demonstrated that neither of these proteins possess UroS activity and the real UroS remains to be identified. This was demonstrated by the failure of codon-optimized genes to complement a definedEscherichia coli hemD−mutant (SASZ31) deficient in UroS activity. Furthermore, HPLC analysis of the oxidized reaction product from recombinant, purifiedP. falciparumHmbS showed that only uroporphyrin I could be detected (corresponding to hydroxymethylbilane production). No uroporphyrin III was detected, showing thatP. falciparumHmbS does not have UroS activity and can only catalyze the formation of hydroxymethylbilane from porphobilinogen.
登录
查看更多内容
寄生虫基因编码的δ-氨基乙酰丙酸合酶参与恶性疟原虫从头合成血红素。
影响因子：
4.1
作者：
S. Varadharajan;S. Dhanasekaran;ZQ Bonday;P. Rangarajan;Govindarajan Padmanaban
通讯作者：
Govindarajan Padmanaban
影响因子：
4.1
作者：
Raux, E;Leech, HK;Warren, MJ
通讯作者：
Warren, MJ
影响因子：
4.8
作者：
Nagaraj, Viswanathan Arun;Arumugam, Rajavel;Padmanaban, Govindarajan
通讯作者：
Padmanaban, Govindarajan
大肠杆菌 K12 的尿卟啉和粪卟啉 I 累积突变体。
DOI：
--
发表时间：
1979
期刊：
Journal of General Microbiology
影响因子：
--
作者：
P. Chartrand;D. Tardif;A. Sasarman
通讯作者：
A. Sasarman
影响因子：
4.1
作者：
ALWAN, AF;MGBEJE, BIA;JORDAN, PM
通讯作者：
JORDAN, PM