Structural basis for selective inhibition of human serine hydroxymethyltransferase by secondary bile acid conjugate.
Structural basis for selective inhibition of human serine hydroxymethyltransferase by secondary bile acid conjugate.
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DOI：
10.1016/j.isci.2021.102036
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发表时间：
2021-02-19
期刊：
影响因子：
5.8
通讯作者：
Sando S
中科院分区：
文献类型：
--
作者：
Ota T;Senoo A;Shirakawa M;Nonaka H;Saito Y;Ito S;Ueno G;Nagatoishi S;Tsumoto K;Sando S
胆汁酸是胆固醇的代谢产物，其促进脂质在小肠中的消化和吸收。胆汁酸作为受体的激动剂来调节其自身的代谢。胆汁酸还调节其他生物系统，如糖代谢，肠道多药耐药性和适应性免疫。然而，胆汁酸的许多生理作用仍然没有确定。在这项研究中，我们解决了人丝氨酸羟甲基转移酶（hSHMT）的晶体结构与内源性二级胆汁酸甘氨酸共轭物的复合物。使用突变分析、生物物理测量和结构-活性关系研究证明了hSHMT和配体之间的特异性相互作用，表明二级胆汁酸缀合物可作为SHMT活性的调节剂。证实了hSHMT与二级胆汁酸甘氨酸结合物复合物的晶体结构，证实了hSHMT与二级胆汁酸结合物之间的特异性相互作用，提出了胆汁酸作为一碳代谢调节剂的生物学作用。
Bile acids are metabolites of cholesterol that facilitate lipid digestion and absorption in the small bowel. Bile acids work as agonists of receptors to regulate their own metabolism. Bile acids also regulate other biological systems such as sugar metabolism, intestinal multidrug resistance, and adaptive immunity. However, numerous physiological roles of bile acids remain undetermined. In this study, we solved the crystal structure of human serine hydroxymethyltransferase (hSHMT) in complex with an endogenous secondary bile acid glycine conjugate. The specific interaction between hSHMT and the ligand was demonstrated using mutational analyses, biophysical measurements, and structure-activity relationship studies, suggesting that secondary bile acid conjugates may act as modulators of SHMT activity. The crystal structures of hSHMT in complex with secondary bile acid glycine conjugate Specific interactions between hSHMT and secondary bile acid conjugate were validated Biological role of bile acids as modulators for one-carbon metabolism is suggested Molecular Interaction; Structural Biology; Metabolic Engineering
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影响因子：
4.6
作者：
Kolhatkar, Vidula;Polli, James E.
通讯作者：
Polli, James E.
DOI：
10.1107/s0907444909052925
发表时间：
2010-02
期刊：
Acta crystallographica. Section D, Biological crystallography
影响因子：
--
作者：
Adams PD;Afonine PV;Bunkóczi G;Chen VB;Davis IW;Echols N;Headd JJ;Hung LW;Kapral GJ;Grosse-Kunstleve RW;McCoy AJ;Moriarty NW;Oeffner R;Read RJ;Richardson DC;Richardson JS;Terwilliger TC;Zwart PH
通讯作者：
Zwart PH
影响因子：
8
作者：
Gupta R;Yang Q;Dogra SK;Wajapeyee N
通讯作者：
Wajapeyee N
DOI：
10.1073/pnas.1706617114
发表时间：
2017-10-24
影响因子：
11.1
作者：
Ducker, Gregory S.;Ghergurovich, Jonathan M.;Rabinowitz, Joshua D.
通讯作者：
Rabinowitz, Joshua D.
影响因子：
4.8
作者：
Kawamata, Y;Fujii, R;Fujino, M
通讯作者：
Fujino, M