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内脏利什曼病和皮肤利什曼病的利什曼原虫属的 UDP-半乳糖吡喃糖变位酶。

UDP-galactopyranose mutases from Leishmania species that cause visceral and cutaneous leishmaniasis.

机构信息

Department of Biochemistry, Virginia Tech, Blacksburg, VA 24061, United States; Fralin Life Science Institute, Virginia Tech, Blacksburg, VA 24061, United States.

出版信息

Arch Biochem Biophys. 2013 Oct 15;538(2):103-10. doi: 10.1016/j.abb.2013.08.014. Epub 2013 Sep 3.

DOI:10.1016/j.abb.2013.08.014
PMID:24012809
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3849806/
Abstract

Leishmaniasis is a vector-borne, neglected tropical disease caused by parasites from the genus Leishmania. Galactofuranose (Galf) is found on the cell surface of Leishmania parasites and is important for virulence. The flavoenzyme that catalyzes the isomerization of UDP-galactopyranose to UDP-Galf, UDP-galactopyranose mutase (UGM), is a validated drug target in protozoan parasites. UGMs from L. mexicana and L. infantum were recombinantly expressed, purified, and characterized. The isolated enzymes contained tightly bound flavin cofactor and were active only in the reduced form. NADPH is the preferred redox partner for both enzymes. A kcat value of 6 ± 0.4s(-1) and a Km value of 252 ± 42 μM were determined for L. infantum UGM. For L. mexicana UGM, these values were ∼4-times lower. Binding of UDP-Galp is enhanced 10-20 fold in the reduced form of the enzymes. Changes in the spectra of the reduced flavin upon interaction with the substrate are consistent with formation of a flavin-iminium ion intermediate.

摘要

利什曼病是一种由利什曼原虫属寄生虫引起的经媒介传播的被忽视的热带病。半乳糖呋喃糖 (Galf) 存在于利什曼原虫寄生虫的细胞表面，对于毒力很重要。催化 UDP-半乳糖吡喃糖向 UDP-Galf 异构化的黄素酶，即 UDP-半乳糖吡喃糖变位酶 (UGM)，是原生动物寄生虫中经过验证的药物靶点。来自 L. mexicana 和 L. infantum 的 UGMs 被重组表达、纯化和表征。分离的酶含有紧密结合的黄素辅因子，仅在还原形式下具有活性。NADPH 是两种酶的首选氧化还原伴侣。L. infantum UGM 的 kcat 值为 6 ± 0.4s(-1)，Km 值为 252 ± 42 μM。对于 L. mexicana UGM，这些值低约 4 倍。在酶的还原形式下，UDP-Galp 的结合增强了 10-20 倍。还原态黄素与底物相互作用时光谱的变化与黄素-亚氨基离子中间物的形成一致。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bbbc/3849806/82a27b68687e/nihms526266f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bbbc/3849806/680710bd2d37/nihms526266f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bbbc/3849806/fddc838495e7/nihms526266f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bbbc/3849806/39be114fe92c/nihms526266f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bbbc/3849806/a7f14a54098c/nihms526266f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bbbc/3849806/73a9e4422734/nihms526266f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bbbc/3849806/1fcb1ecb1f50/nihms526266f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bbbc/3849806/82a27b68687e/nihms526266f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bbbc/3849806/680710bd2d37/nihms526266f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bbbc/3849806/fddc838495e7/nihms526266f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bbbc/3849806/39be114fe92c/nihms526266f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bbbc/3849806/a7f14a54098c/nihms526266f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bbbc/3849806/73a9e4422734/nihms526266f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bbbc/3849806/1fcb1ecb1f50/nihms526266f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bbbc/3849806/82a27b68687e/nihms526266f7.jpg

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Identification of the NAD(P)H binding site of eukaryotic UDP-galactopyranose mutase.鉴定真核 UDP-半乳糖吡喃糖变位酶的 NAD(P)H 结合位点。
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