RmlC, the third enzyme of dTDP-L-rhamnose pathway, is a new class of epimerase

Giraud MF.; Field RA.; Berlind C.; Naismith JH.; Leonard GA.

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RmlC, the third enzyme of dTDP-L-rhamnose pathway, is a new class of epimerase

机译：RmlC是dTDP-L-鼠李糖途径的第三种酶，是一类新型的差向异构酶

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Deoxythymidine diphosphate (dTDP)-L-rhamnose is the precursor of L-rhamnose, a saccharide required for the virulence of some pathogenic bacteria. dTDP-L-rhamnose is synthesized from glucose-l-phosphate and deoxythymidine triphosphate (dTTP) via a pathway involving four distinct enzymes. This pathway does not exist in humans and the enzymes involved in dTDP-L-rhamnose synthesis are potential targets for the design of new therapeutic agents. Here, the crystal structure of dTDP-6-deoxy-D-xylo-4-hexulose 3,5 epimerase (RmlC, EC5.1.3.13) from Salmonella enterica serovar Typhimurium was determined. The third enzyme of the rhamnose biosynthetic pathway, RmlC epimerizes at two carbon centers, the 3 and 5 positions of the sugar ring. The structure was determined by multiwavelength anomalous diffraction to a resolution of 2.17 Angstrom. RmlC is a dimer and each monomer is formed mainly from two beta-sheets arranged in a beta-sandwich. The structure of a dTDP-phenol-RmlC complex shows the substrate-binding site to be located between the two beta-sheets; this site is formed from residues of both monomers. Sequence alignments of other RmlC enzymes confirm that this region is very highly conserved. The enzyme is distinct structurally from other epimerases known and thus, is the first example of a new class of carbohydrate epimerase. [References: 32]

机译：脱氧胸苷二磷酸（dTDP）-L-鼠李糖是L-鼠李糖的前体，L-鼠李糖是某些致病细菌的毒性所必需的糖。 dTDP-L-鼠李糖由葡萄糖-1-磷酸和脱氧胸苷三磷酸（dTTP）通过涉及四种不同酶的途径合成。该途径在人类中不存在，与dTDP-L-鼠李糖合成有关的酶是设计新治疗剂的潜在目标。在此，确定了来自肠炎沙门氏菌血清型鼠伤寒沙门氏菌的dTDP-6-脱氧-D-xylo-4-己糖3,5差向异构酶的晶体结构（RmlC，EC5.1.3.13）。鼠李糖生物合成途径中的第三个酶RmlC在两个碳中心（糖环的3和5位）上差向异构。该结构是通过多波长异常衍射确定的，分辨率为2.17埃。 RmlC是二聚体，每种单体主要由排列在β-三明治中的两个β-折叠形成。 dTDP-苯酚-RmlC复合物的结构显示底物结合位点位于两个β-折叠之间。该位点由两种单体的残基形成。其他RmlC酶的序列比对证实该区域非常保守。该酶在结构上与已知的其他差向异构酶不同，因此是新型碳水化合物差向异构酶的第一个实例。 [参考：32]

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《Nature structural biology》 |2000年第5期|共5页
作者
Giraud MF.; Field RA.; Berlind C.; Naismith JH.; Leonard GA.;
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正文语种 eng
中图分类生物科学;
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Serovar typhimurium; Streptococcus-suis; Escherichia-coli; Vibrio-cholerae; Biosynthesis; 4-epimerase; Mutants;

机译：鼠伤寒沙门氏菌;猪链球菌;大肠杆菌;霍乱弧菌;生物合成;4-表异构酶;突变体;

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专利

1. RmlC, the third enzyme of dTDP-L-rhamnose pathway, is a new class of epimerase [J] . Giraud MF., Field RA., Berlind C., Nature structural biology . 2000,第5期

机译：RmlC是dTDP-L-鼠李糖途径的第三种酶，是一类新型的差向异构酶
2. Identification of triazinoindol-benzimidazolones as nanomolar inhibitors of the Mycobacterium tuberculosis enzyme TDP-6-deoxy-d-xylo-4-hexopyranosid-4-ulose 3,5-epimerase (RmlC). [J] . Sivendran S, Jones V, Sun Bioorganic and medicinal chemistry . 2010,第2期

机译：三唑吲哚 - 苯并咪唑酮作为结核分枝杆菌酶TDP-6-脱氧-D-Xylo-4-六羟基磷脂-4- ullose 3,5-映异构酶（RMLC）的纳米摩尔抑制剂。
3. Identification of triazinoindol-benzimidazolones as nanomolar inhibitors of the Mycobacterium tuberculosis enzyme TDP-6-deoxy-d-xylo-4-hexopyranosid-4-ulose 3,5-epimerase (RmlC). [J] . Sivendran S, Jones V, Sun Bioorganic and medicinal chemistry . 2010,第2期

机译：三唑吲哚 - 苯并咪唑酮作为结核分枝杆菌酶TDP-6-脱氧-D-Xylo-4-六羟基磷脂-4- ullose 3,5-映异构酶（RMLC）的纳米摩尔抑制剂。
4. Parsimony and Diversity in Enzyme Evolution Revealed by Structural Studies on the Shikimate Pathway Enzymes [C] . John R. Coggins International symposium on mechanisms of enzymatic catalysis . 1998

机译：通过对Shikimate途径酶的结构研究揭示了酶进化中的简约性和多样性。
5. Structural and metabolic studies of the enzyme UDP-galactose 4'-epimerase, associated with the inherited metabolic disorder, galactosemia [D] . Schulz, Jenny Michele. 2004

机译：UDP-半乳糖4'-表异构酶酶的结构和代谢研究，与遗传性代谢疾病半乳糖血症有关
6. Identification of triazinoindol-benzimidazolones as nanomolar inhibitors of the Mycobacterium tuberculosis enzyme TDP-6-deoxy-D-xylo-4-hexopyranosid-4-ulose 35-epimerase (RmlC) [O] . Sharmila Sivendran, Victoria Jones, Dianqing Sun, -1

机译：鉴定三嗪醛 - 苯并咪唑酮作为结核分枝杆菌纳米摩尔抑制剂TDP-6-脱氧-d-Xylo-4-六丙嘧啶-4- ullose 35-ePimerase（RMLC）
7. The Position of a Key Tyrosine in dTDP-4-Keto-6-deoxy-D- glucose-5-epimerase (EvaD) Alters the Substrate Profile for This RmlC-like Enzyme* [O] . 2015

机译：关键酪氨酸在dTDp-4-Keto-6-deoxy-D-葡萄糖-5-差向异构酶（EvaD）中的位置改变了该RmlC样酶的底物谱*

RmlC, the third enzyme of dTDP-L-rhamnose pathway, is a new class of epimerase

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