Ligand binding phenomena that pertain to the metabolic function of renalase.
Ligand binding phenomena that pertain to the metabolic function of renalase.
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与肾酶代谢功能有关的配体结合现象。
DOI：
10.1016/j.abb.2016.10.011
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发表时间：
2016-12-15
影响因子：
3.9
通讯作者：
Moran GR
中科院分区：
文献类型：
--
作者：
Beaupre BA;Roman JV;Hoag MR;Meneely KM;Silvaggi NR;Lamb AL;Moran GR
肾酶催化β-NAD（P）H异构体（在烟酰胺碱的2或6位携带氢化物）氧化形成β-NAD（P）+。这种活性被认为减轻了这些异构体对初级和次级代谢的多种β-NAD（P）依赖性酶的抑制。在这里，我们提出了各种相关的肾酶功能的配体结合现象的证据。我们提供的证据表明，与6-二氢NAD异构体结合的苹果酸脱氢酶和乳酸脱氢酶的结构具有抑制初级代谢的潜力。先前观察到的肾酶从假单胞菌NAD衍生的底物比那些来自NADP的偏好是由酶与NADPH复合的结构。我们还表明，烟酰胺核苷和mononucloetides减少在2-和6-位置是肾酶底物，但结合弱。在ADP存在下，观察到人肾酶对6-二氢烟酰胺核苷的采集（kred/Kd）增加了7倍。然而，一般来说，添加补体配体，ADP的单核苷酸或AMP的核苷底物，没有增强还原半反应。非底物烟酰胺核苷或核苷酸结合较弱，表明只有β-NADH和β-NADPH与二核苷酸底物竞争进入活性位点。
Renalase catalyzes the oxidation of isomers of β-NAD(P)H that carry the hydride in the 2 or 6 positions of the nicotinamide base to form β-NAD(P)+. This activity is thought to alleviate inhibition of multiple β-NAD(P)-dependent enzymes of primary and secondary metabolism by these isomers. Here we present evidence for a variety of ligand binding phenomena relevant to the function of renalase. We offer evidence of the potential for primary metabolism inhibition with structures of malate dehydrogenase and lactate dehydrogenase bound to the 6-dihydroNAD isomer. The previously observed preference of renalase from Pseudomonas for NAD-derived substrates over those derived from NADP is accounted for by the structure of the enzyme in complex with NADPH. We also show that nicotinamide nucleosides and mononucloetides reduced in the 2- and 6-positions are renalase substrates, but bind weakly. A seven-fold enhancement of acquisition (kred/Kd) for 6-dihydronicotinamide riboside was observed for human renalase in the presence of ADP. However, generally the addition of complement ligands, ADP for mononucloetide or AMP for nucleoside substrates, did not enhance the reductive half-reaction. Non-substrate nicotinamide nucleosides or nucleotides bind weakly suggesting that only β-NADH and β-NADPH compete with dinucleotide substrates for access to the active site.
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DOI：
10.1107/s0907444904019158
发表时间：
2004-12-01
影响因子：
2.2
作者：
Emsley, P;Cowtan, K
通讯作者：
Cowtan, K
影响因子：
5.6
作者：
Milani, Mario;Ciriello, Francesco;Aliverti, Alessandro
通讯作者：
Aliverti, Alessandro
DOI：
10.1107/s0907444910026582
发表时间：
2010-11-01
影响因子：
2.2
作者：
Afonine, Pavel V.;Mustyakimov, Marat;Adams, Paul D.
通讯作者：
Adams, Paul D.
影响因子：
7.3
作者：
Kohlmann, Anna;Zech, Stephan G.;Dalgarno, David C.
通讯作者：
Dalgarno, David C.
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