Unsaturated Lipid Assimilation by Mycobacteria Requires Auxiliary cis-trans Enoyl CoA Isomerase.
Unsaturated Lipid Assimilation by Mycobacteria Requires Auxiliary cis-trans Enoyl CoA Isomerase.
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DOI：
10.1016/j.chembiol.2015.10.009
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发表时间：
2015-12
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通讯作者：
Sonali Srivastava;Sonali Srivastava;S. Chaudhary;Lipi Thukral;C. Shi;R. Gupta;Radhika Gupta;Radhika Gupta;K. Priyadarshan;A. Vats;A. S. Haque;R. Sankaranarayanan;Vivek T. Natarajan;Vivek T. Natarajan;Rakesh Sharma;C. Aldrich;R. Gokhale;R. Gokhale
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作者：
Sonali Srivastava;Sonali Srivastava;S. Chaudhary;Lipi Thukral;C. Shi;R. Gupta;Radhika Gupta;Radhika Gupta;K. Priyadarshan;A. Vats;A. S. Haque;R. Sankaranarayanan;Vivek T. Natarajan;Vivek T. Natarajan;Rakesh Sharma;C. Aldrich;R. Gokhale;R. Gokhale
结核分枝杆菌（Mtb）可以通过吸收宿主来源的脂肪酸的能量在缺氧坏死组织中存活。虽然β-氧化辅助酶的扩展库被认为是至关重要的形式适应性，但描述它们的功能相关性一直具有挑战性。在这里，我们证明了脂肪酸降解（FadAB）复合物不能选择性地分解顺式脂肪酰基底物。我们证明了脂肪酰基底物在theMtbFadB口袋中的立体选择性结合是由于来自Phe287残基的空间位阻。通过开发功能筛选，我们将mtbech蛋白家族分类为单功能或双功能酶，其中三种酶与FadAB复合物互补以降解脂肪酸。双环转烯酰基辅酶A （CoA）异构酶的晶体结构测定揭示了活性位点残基在Ech酶中的独特位置。因此，我们的研究揭示了脂质重塑酶的多功能性，并确定了独立的单酰基辅酶a异构体酶在分枝杆菌生物学中的重要作用。
Mycobacterium tuberculosis(Mtb) can survive in hypoxic necrotic tissue by assimilating energy from host-derived fatty acids. While the expanded repertoire of β-oxidation auxiliary enzymes is considered crucial forMtbadaptability, delineating their functional relevance has been challenging. Here, we show that theMtbfatty acid degradation (FadAB) complex cannot selectively break downcisfatty acyl substrates. We demonstrate that the stereoselective binding of fatty acyl substrates in theMtbFadB pocket is due to the steric hindrance from Phe287 residue. By developing a functional screen, we classify the family ofMtbEch proteins as monofunctional or bifunctional enzymes, three of which complement the FadAB complex to degradecisfatty acids. Crystal structure determination of twocis-transenoyl coenzyme A (CoA) isomerases reveals distinct placement of active-site residue in Ech enzymes. Our studies thus reveal versatility ofMtblipid-remodeling enzymes and identify an essential role of stand-alonecis-transenoyl CoA isomerases in mycobacterial biology.