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.
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DOI：
10.1099/mic.0.001095
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发表时间：
2021-10
期刊：
影响因子：
--
通讯作者：
Warren MJ
中科院分区：
文献类型：
--
作者：
Scott AF;Deery E;Lawrence AD;Warren MJ
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鉴定，但已表明该活性位于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。密码子优化的基因未能补充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，来自重组、纯化的恶性疟原虫HmbS的氧化反应产物的HPLC分析表明，仅可以检测到尿卟啉I（对应于羟甲基胆烷的产生）。没有检测到尿卟啉III，表明恶性疟原虫HmbS不具有UroS活性，并且只能催化由卟啉胆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 in Plasmodium 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 defined Escherichia coli hemD − mutant (SASZ31) deficient in UroS activity. Furthermore, HPLC analysis of the oxidized reaction product from recombinant, purified P. falciparum HmbS showed that only uroporphyrin I could be detected (corresponding to hydroxymethylbilane production). No uroporphyrin III was detected, showing that P. falciparum HmbS does not have UroS activity and can only catalyze the formation of hydroxymethylbilane from porphobilinogen.
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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
DOI：
10.1016/0006-291x(92)91258-r
发表时间：
1992-09-16
影响因子：
3.1
作者：
SUROLIA, N;PADMANABAN, G
通讯作者：
PADMANABAN, G
影响因子：
3.9
作者：
Heinemann, Ilka U.;Jahn, Martina;Jahn, Dieter
通讯作者：
Jahn, Dieter
DOI：
10.1039/p19820002427
发表时间：
1982-01-01
期刊：
JOURNAL OF THE CHEMICAL SOCIETY-PERKIN TRANSACTIONS 1
影响因子：
--
作者：
BATTERSBY, AR;FOOKES, CJR;MATCHAM, GWJ
通讯作者：
MATCHAM, GWJ