Kinetic Analysis of PRMT1 Reveals Multifactorial Processivity and a Sequential Ordered Mechanism

机译：PRMT1的动力学分析显示了多因素处理能力和顺序有序机制

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Abstract > Arginine methylation is a prevalent post‐translational modification in eukaryotic cells. Two significant debates exist within the field: do these enzymes dimethylate their substrates in a processive or distributive manner, and do these enzymes operate using a random or sequential method of bisubstrate binding? We revealed that human protein arginine N ‐methyltransferase?1 (PRMT1) enzyme kinetics are dependent on substrate sequence. Further, peptides containing an N η‐hydroxyarginine generally demonstrated substrate inhibition and had improved K <sub>M</sub> values, which evoked a possible role in inhibitor design. We also revealed that the perceived degree of enzyme processivity is a function of both cofactor and enzyme concentration, suggesting that previous conclusions about PRMT sequential methyl transfer mechanisms require reassessment. Finally, we demonstrated a sequential ordered Bi–Bi kinetic mechanism for PRMT1, based on steady‐state kinetic analysis. Together, our data indicate a PRMT1 mechanism of action and processivity that might also extend to other functionally and structurally conserved PRMTs. </abstract> </span> <span class="z_kbtn z_kbtnclass hoverxs" style="display: none;">展开▼</span> </div> <div class="translation abstracttxt"> <span class="zhankaihshouqi fivelineshidden" id="abstract"> <span>机译：</span><Abstract Type =“Main”XML：Lang =“en”> <标题类型=“main”>摘要</标题> >精氨酸甲基化是真核细胞中的普遍翻译后修饰。现场内存在两种重大辩论：这些酶以加工或分配方式对它们的基材二甲烷化盐，并使用随机或连续的双向绑定方法进行操作吗？我们透露，人蛋白质精氨酸 N </ i> - 甲基转移酶α1（PRMT1）酶动力学依赖于基质序列。此外，含有αn-羟基喹啉素的肽通常证明底物抑制，并改善了 k / k> <sub> m </ sub>值，这引起了抑制剂设计中可能的作用。我们还透露，感知的酶处理程度是辅助因子和酶浓度的函数，表明前一种结论是关于PRMT序列甲基转移机制需要重新评估。最后，我们证明了基于稳态动力学分析的PRMT1的顺序有序的Bi-Bi动机机制。我们的数据在一起表示可能还延伸到其他功能和结构上保守的PRMTS的动作和处理能力的PRMT1机制。 </ p> </ abstract> </span> <span class="z_kbtn z_kbtnclass hoverxs" style="display: none;">展开▼</span> </div> </div> <div class="record"> <h2 class="all_title" id="enpatent33" >著录项</h2> <ul> <li> <span class="lefttit">来源</span> <div style="width: 86%;vertical-align: text-top;display: inline-block;"> <a href='/journal-foreign-16039/'>《Chembiochem: A European journal of chemical biology》</a> <b style="margin: 0 2px;">|</b><span>2018年第1期</span><b style="margin: 0 2px;">|</b><span>共15页</span> </div> </li> <li> <div class="author"> <span class="lefttit">作者</span> <p id="fAuthorthree" class="threelineshidden zhankaihshouqi"> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Brown Jennifer I.&option=202" target="_blank" rel="nofollow">Brown Jennifer I.;</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Koopmans Timo&option=202" target="_blank" rel="nofollow">Koopmans Timo;</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=van?Strien Jolinde&option=202" target="_blank" rel="nofollow">van?Strien Jolinde;</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Martin Nathaniel I.&option=202" target="_blank" rel="nofollow">Martin Nathaniel I.;</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Frankel Adam&option=202" target="_blank" rel="nofollow">Frankel Adam;</a> </p> <span class="z_kbtnclass z_kbtnclassall hoverxs" id="zkzz" style="display: none;">展开▼</span> </div> </li> <li> <div style="display: flex;"> <span class="lefttit">作者单位</span> <div style="position: relative;margin-left: 3px;max-width: 639px;"> <div class="threelineshidden zhankaihshouqi" id="fOrgthree"> <p>Faculty of Pharmaceutical SciencesUniversity of British Columbia2405 Wesbrook Mall Vancouver BC V6T 1Z3 Canada;</p> <p>Department of Chemical Biology and Drug DiscoveryUniversity of Utrecht3584 CG Utrecht The Netherlands;</p> <p>Leiden Institute for ChemistryGorlaeus LaboratoriesEinsteinweg 55 2333CC Leiden The Netherlands;</p> <p>Department of Chemical Biology and Drug DiscoveryUniversity of Utrecht3584 CG Utrecht The Netherlands;</p> <p>Faculty of Pharmaceutical SciencesUniversity of British Columbia2405 Wesbrook Mall Vancouver BC V6T 1Z3 Canada;</p> </div> <span class="z_kbtnclass z_kbtnclassall hoverxs" id="zhdw" style="display: none;">展开▼</span> </div> </div> </li> <li > <span class="lefttit">收录信息</span> <span style="width: 86%;vertical-align: text-top;display: inline-block;"></span> </li> <li> <span class="lefttit">原文格式</span> <span>PDF</span> </li> <li> <span class="lefttit">正文语种</span> <span>eng</span> </li> <li> <span class="lefttit">中图分类</span> <span><a href="https://www.zhangqiaokeyan.com/clc/179.html" title="分子生物学">分子生物学;</a></span> </li> <li class="antistop"> <span class="lefttit">关键词</span> <p style="width: 86%;vertical-align: text-top;"> <a style="color: #3E7FEB;" href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=enzyme catalysis&option=203" rel="nofollow">enzyme catalysis;</a> <a style="color: #3E7FEB;" href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=kinetics&option=203" rel="nofollow">kinetics;</a> <a style="color: #3E7FEB;" href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=peptides&option=203" rel="nofollow">peptides;</a> <a style="color: #3E7FEB;" href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=protein modifications&option=203" rel="nofollow">protein modifications;</a> <a style="color: #3E7FEB;" href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=transferases&option=203" rel="nofollow">transferases;</a> </p> <div class="translation"> 机译：酶催化;动力学;肽;蛋白质修饰;转移酶; </div> </li> </ul> </div> </div> <div class="literature cardcommon"> <div class="similarity "> <h3 class="all_title" id="enpatent66">相似文献</h3> <div class="similaritytab clearfix"> <ul> <li class="active" >外文文献</li> <li >中文文献</li> <li >专利</li> </ul> </div> <div class="similarity_details"> <ul > <li> <div> <b>1. </b><a class="enjiyixqcontent" href="/journal-foreign-detail/0704022055544.html">Kinetic Analysis of PRMT1 Reveals Multifactorial Processivity and a Sequential Ordered Mechanism</a> <b>[J]</b> . <span> <a 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