X-ray free-electron laser studies reveal correlated motion during isopenicillin N synthase catalysis.
X-ray free-electron laser studies reveal correlated motion during isopenicillin N synthase catalysis.
复制标题
DOI：
10.1126/sciadv.abh0250
复制
发表时间：
2021-08
期刊：
影响因子：
13.6
通讯作者：
Schofield CJ
中科院分区：
文献类型：
--
作者：
Rabe P;Kamps JJAG;Sutherlin KD;Linyard JDS;Aller P;Pham CC;Makita H;Clifton I;McDonough MA;Leissing TM;Shutin D;Lang PA;Butryn A;Brem J;Gul S;Fuller FD;Kim IS;Cheah MH;Fransson T;Bhowmick A;Young ID;O'Riordan L;Brewster AS;Pettinati I;Doyle M;Joti Y;Owada S;Tono K;Batyuk A;Hunter MS;Alonso-Mori R;Bergmann U;Owen RL;Sauter NK;Claridge TDW;Robinson CV;Yachandra VK;Yano J;Kern JF;Orville AM;Schofield CJ
互补的XFEL方法揭示了异青霉素N合成酶催化过程中的O2反应中间产物和全球蛋白质动力学。异青霉素N合成酶(IPNS)催化L-δ-(α-氨基己二酰基-L-半胱氨基-D-缬氨酸(ACV)与氧气发生独特的反应，产生了异青霉素N(IPN)，它是所有天然青霉素和头孢菌素的前体。X射线自由电子激光研究包括时间分辨结晶学和发射光谱，揭示了IPNS：Fe(II)：ACV如何与氧气反应生成Fe(III)超氧化物，导致活性中心体积的差异和意外的构象变化，并传播到结构偏远的区域。结合溶液研究，结果揭示了蛋白质动力学在ACV向IPN转化过程中调节中间构象的重要性。这些结果对多种IPNS相关加氧酶的催化作用有影响，包括那些参与人类缺氧反应的加氧酶，并突显了系列飞秒结晶学的力量，可以提供对反应过程中远程酶动力学的洞察，目前非蛋白质催化剂是不可能的。
Complementary XFEL methods reveal O2 reaction intermediates and global protein dynamics during Isopenicillin N synthase catalysis. Isopenicillin N synthase (IPNS) catalyzes the unique reaction of l-δ-(α-aminoadipoyl)-l-cysteinyl-d-valine (ACV) with dioxygen giving isopenicillin N (IPN), the precursor of all natural penicillins and cephalosporins. X-ray free-electron laser studies including time-resolved crystallography and emission spectroscopy reveal how reaction of IPNS:Fe(II):ACV with dioxygen to yield an Fe(III) superoxide causes differences in active site volume and unexpected conformational changes that propagate to structurally remote regions. Combined with solution studies, the results reveal the importance of protein dynamics in regulating intermediate conformations during conversion of ACV to IPN. The results have implications for catalysis by multiple IPNS-related oxygenases, including those involved in the human hypoxic response, and highlight the power of serial femtosecond crystallography to provide insight into long-range enzyme dynamics during reactions presently impossible for nonprotein catalysts.
登录
查看更多内容
影响因子：
48
作者：
Fuller FD;Gul S;Chatterjee R;Burgie ES;Young ID;Lebrette H;Srinivas V;Brewster AS;Michels-Clark T;Clinger JA;Andi B;Ibrahim M;Pastor E;de Lichtenberg C;Hussein R;Pollock CJ;Zhang M;Stan CA;Kroll T;Fransson T;Weninger C;Kubin M;Aller P;Lassalle L;Bräuer P;Miller MD;Amin M;Koroidov S;Roessler CG;Allaire M;Sierra RG;Docker PT;Glownia JM;Nelson S;Koglin JE;Zhu D;Chollet M;Song S;Lemke H;Liang M;Sokaras D;Alonso-Mori R;Zouni A;Messinger J;Bergmann U;Boal AK;Bollinger JM Jr;Krebs C;Högbom M;Phillips GN Jr;Vierstra RD;Sauter NK;Orville AM;Kern J;Yachandra VK;Yano J
通讯作者：
Yano J
影响因子：
16.6
作者：
Gisriel, Chris;Coe, Jesse;Zatsepin, Nadia A.
通讯作者：
Zatsepin, Nadia A.
影响因子：
35
作者：
Emma, P.;Akre, R.;Galayda, J.
通讯作者：
Galayda, J.
影响因子：
48
作者：
Hattne, Johan;Echols, Nathaniel;Rosalie Tran;Kern, Jan;Gildea, Richard J.;Brewster, Aaron S.;Alonso-Mori, Roberto;Gloeckner, Carina;Hellmich, Julia;Laksmono, Hartawan;Sierra, Raymond G.;Lassalle-Kaiser, Benedikt;Lampe, Alyssa;Han, Guangye;Gul, Sheraz;DiFiore, Doerte;Milathianaki, Despina;Fry, Alan R.;Miahnahri, Alan;White, William E.;Schafer, Donald W.;Seibert, M. Marvin;Koglin, Jason E.;Sokaras, Dimosthenis;Weng, Tsu-Chien;Sellberg, Jonas;Latimers, Matthew J.;Glatzel, Pieter;Zwart, Petrus H.;Grosse-Kunstleve, Ralf W.;Bogan, Michael J.;Messerschmidt, Marc;Williams, Garth J.;Boutet, Sebastien;Messinger, Johannes;Zouni, Athina;Yano, Junko;Bergmann, Uwe;Yachandra, Vittal K.;Adams, Paul D.;Sauter, Nicholas K.
通讯作者：
Sauter, Nicholas K.
影响因子：
5.7
作者：
Chowdhury, Rasheduzzaman;McDonough, Michael A.;Schofield, Christopher J.
通讯作者：
Schofield, Christopher J.