LRE1
目录号 : GC33296
LRE1是可溶性腺苷酸环化酶的特异性和变构抑制剂。
Cas No.:1252362-53-0
Sample solution is provided at 25 µL, 10mM.
;)
,-1-7$$$37316672.jpg');)
;)
;)
$$$36806353.jpg');)
;33(7)%EF%BC%9A546-561$$$37156877.jpg');)
;)
;)
;)
%201124-1138.$$$35908550.jpg');)
%20766-780.$$$37100057.jpg');)
%20418-432.$$$36893736.jpg');)
%EF%BC%9A-240-255.$$$35108512.jpg');)
533-545$$$36543525.jpg');)
%201-13.$$$36600053.jpg');)
;)
Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
LRE1 is a specific and allosteric inhibitor of soluble adenylyl cyclase.
LRE1 binds to the bicarbonate activator binding site and inhibits soluble adenylyl cyclase (sAC) via a unique allosteric mechanism[1]. LRE1 prevents sAC-dependent processes in cellular and physiological systems and facilitates exploration of the therapeutic potential of sAC inhibition[1].LRE1 (0.5-100 μM, 60 minutes ) inhibits sperm and mitochondrial functions of sAC[1].|| Western Blot Analysis[1]||Cell Line:|Mouse cauda sperm|Concentration:|0.5-100 µM|Incubation Time:|60 minutes |Result:|LRE1 inhibits sAC dependent sperm capacitation[1].
[1]. Ramos-Espiritu L, et al. Discovery of LRE1 as a specific and allosteric inhibitor of soluble adenylyl cyclase. Nat Chem Biol. 2016 Oct;12(10):838-44.
| Cas No. | 1252362-53-0 | SDF | |
| Canonical SMILES | NC1=NC(N(CC2=CC=CS2)C3CC3)=CC(Cl)=N1 | ||
| 分子式 | C12H13ClN4S | 分子量 | 280.78 |
| 溶解度 | DMSO: 125 mg/mL (445.19 mM) | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
||
| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
 |
1 mg | 5 mg | 10 mg |
| 1 mM | 3.5615 mL | 17.8075 mL | 35.6151 mL |
| 5 mM | 0.7123 mL | 3.5615 mL | 7.123 mL |
| 10 mM | 0.3562 mL | 1.7808 mL | 3.5615 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
LRE1 directly inhibits the NDR/Lats kinase Cbk1 at the cell division site in a phosphorylation-dependent manner
Curr Biol 2013 Sep 23;23(18):1736-45.PMID:23954433DOI:10.1016/j.cub.2013.07.032.
Background: The nuclear Dbf2 related (NDR) family of protein kinases play important roles in cell-cycle regulation, apoptosis, cell morphogenesis, and development in a variety of organisms. In budding yeast, the NDR kinase complex composed of Cbk1 and its regulatory subunit, Mob2, have an established role in the control of cell separation/abscission that follows cytokinesis. Whereas the activators of Cbk1-Mob2 have been more extensively described, the mechanisms that restrict or inhibit Cbk1-Mob2 catalytic activity remain largely unknown. Results: We identified the protein LRE1 as a direct inhibitor of Cbk1-Mob2 catalytic activity. We show that LRE1 accumulates at the cell division site in late anaphase and associates with both Mob2 and Cbk1 in vivo and in vitro. Biochemical and functional analysis established that the ability of LRE1 to associate with Cbk1-Mob2 was reduced by mitotic Cdk1 activity and promoted by Cdc14 phosphatase at the end of mitosis. The inhibition of Cbk1-Mob2 by LRE1 was critical to promote the survival of cells lacking the actomyosin driven pathway of cytokinesis. Conclusions: We established LRE1 as a direct inhibitor of the NDR kinase Cbk1-Mob2, which is regulated in a cell-cycle-dependent manner. We propose that similar inhibitory proteins may also provide fine tuning for the activity of NDR kinases in other organisms.
LRE1 affects chitinase expression, trehalose accumulation and heat resistance through inhibition of the Cbk1 protein kinase in Saccharomyces cerevisiae
Mol Microbiol 2001 Sep;41(6):1311-26.PMID:11580836DOI:10.1046/j.1365-2958.2001.02590.x.
The addition of glucose to derepressed cells of the yeast Saccharomyces cerevisiae triggers activation of the cAMP pathway with a rapid drop in stress resistance as a consequence. We have isolated the LRE1 gene as a multicopy suppressor of glucose-induced loss of heat resistance. Overexpression of LRE1 in a wild-type strain causes the same phenotype as observed in strains with reduced activity of the cAMP-PKA pathway: higher heat resistance and enhanced trehalose levels. Deletion of LRE1 results in the opposite phenotypes. Epistasis analysis indicates that these effects are independent of cAMP and PKA, of the protein kinases Yak1, Sch9 and Rim15 and of the transcription factors Msn2 and Msn4. LRE1 has recently been isolated in a two-hybrid screen using the conserved protein kinase Cbk1 as a bait. Cbk1 controls the expression of CTS1 (encoding chitinase) through the transcription factor Ace2. We demonstrate here that overexpression of LRE1 represses CTS1 whereas deletion of LRE1 induces the expression of CTS1. Repression of CTS1 results in deficient cell separation as a result of inefficient degradation of the chitin ring after cytokinesis. Neither deletion nor overexpression of LRE1 has any effect on CTS1 expression in a cbk1Delta mutant, indicating that LRE1 inhibits Cbk1. In addition, we show that increased trehalose accumulation and increased heat resistance caused by overexpression of LRE1 are also the result of inhibition of Cbk1, revealing a novel control pathway for certain targets affected by PKA. The yeast genome contains a homologue of LRE1, YDR528w, which we have called HLR1 (for homologue of LRE1). Deletion and overexpression of HLR1 causes similar but less pronounced effects compared with LRE1.
Discovery of LRE1 as a specific and allosteric inhibitor of soluble adenylyl cyclase
Nat Chem Biol 2016 Oct;12(10):838-44.PMID:27547922DOI:10.1038/nchembio.2151.
The prototypical second messenger cAMP regulates a wide variety of physiological processes. It can simultaneously mediate diverse functions by acting locally in independently regulated microdomains. In mammalian cells, two types of adenylyl cyclase generate cAMP: G-protein-regulated transmembrane adenylyl cyclases and bicarbonate-, calcium- and ATP-regulated soluble adenylyl cyclase (sAC). Because each type of cyclase regulates distinct microdomains, methods to distinguish between them are needed to understand cAMP signaling. We developed a mass-spectrometry-based adenylyl cyclase assay, which we used to identify a new sAC-specific inhibitor, LRE1. LRE1 bound to the bicarbonate activator binding site and inhibited sAC via a unique allosteric mechanism. LRE1 prevented sAC-dependent processes in cellular and physiological systems, and it will facilitate exploration of the therapeutic potential of sAC inhibition.
The Soluble Adenylyl Cyclase Inhibitor LRE1 Prevents Hepatic Ischemia/Reperfusion Damage Through Improvement of Mitochondrial Function
Int J Mol Sci 2020 Jul 11;21(14):4896.PMID:32664470DOI:10.3390/ijms21144896.
Hepatic ischemia/reperfusion (I/R) injury is a leading cause of organ dysfunction and failure in numerous pathological and surgical settings. At the core of this issue lies mitochondrial dysfunction. Hence, strategies that prime mitochondria towards damage resilience might prove applicable in a clinical setting. A promising approach has been to induce a mitohormetic response, removing less capable organelles, and replacing them with more competent ones, in preparation for an insult. Recently, a soluble form of adenylyl cyclase (sAC) has been shown to exist within mitochondria, the activation of which improved mitochondrial function. Here, we sought to understand if inhibiting mitochondrial sAC would elicit mitohormesis and protect the liver from I/R injury. Wistar male rats were pretreated with LRE1, a specific sAC inhibitor, prior to the induction of hepatic I/R injury, after which mitochondria were collected and their metabolic function was assessed. We find LRE1 to be an effective inducer of a mitohormetic response based on all parameters tested, a phenomenon that appears to require the activity of the NAD+-dependent sirtuin deacylase (SirT3) and the subsequent deacetylation of mitochondrial proteins. We conclude that LRE1 pretreatment leads to a mitohormetic response that protects mitochondrial function during I/R injury.
Multiple copies of PBS2, MHP1 or LRE1 produce glucanase resistance and other cell wall effects in Saccharomyces cerevisiae
Yeast 1997 Mar 15;13(3):199-213.PMID:9090049DOI:10.1002/(SICI)1097-0061(19970315)13:3<199::AID-YEA76>3.0.CO;2-Z.
Five sequences were isolated by selection for multiple copy plasmids that conferred resistance to laminarinase, an enzyme that specifically degrades cell wall beta(1-3) glucan linkages. Strains carrying three of these plasmids showed alterations in cell wall glucan labelling. One of these plasmids carried PBS2, a previously identified, non-essential gene which produces a variety of phenotypes and encodes a mitogen-activated protein kinase kinase analogue (Boguslawski and Polazzi, 1987). Cells carrying PBS2 at multiple copy show a small decrease in cell wall beta(1-6) glucans. Measurements of beta(1-3) glucan synthase activity in multi-copy PBS2 cells showed an approximate 30-45% increase in enzyme specific activity while a pbs2 delta disruption strain showed a decrease in glucan synthase activity of approximately 45% relative to control. A pbs2 delta disruption strain was laminarinase super-sensitive and supersensitive to K1 killer toxin while a strain carrying PBS2 at multiple copy was resistant to killer toxin. A second plasmid carried a portion of the MHP1 gene which has been reported to encode a microtubule-interacting protein (Irminger-Finger et al., 1996). The MHP1 gene product is a predicted 1398 amino acid protein and only approximately 80% of the amino portion of this protein is required for laminarinase resistance. Cells carrying the amino portion of MHP1 at multiple copy show a decrease in high molecular weight cell wall beta(1-6) glucans and were killer toxin resistant while a disruption strain was viable and killer toxin super-sensitive. Cells carrying this plasmid showed decreased levels of high molecular weight beta(1-6) glucans and increased glucan synthase activity. The laminarinase resistance conferred by the third plasmid mapped to the previously uncharacterized YCL051W open reading frame and this gene was therefore named LRE1 (laminarinase resistance). The LRE1 gene encodes a non-essential 604 amino acid hydrophilic protein. Unexpectedly, cells carrying LRE1 at multiple copy show no alteration in cell wall glucans or glucan synthase activity. Subcloning experiments demonstrated that the production of these cell wall effects requires the presence of both LRE1 and YCL052C (PBN1), a second open reading frame present on the original plasmid. Cells carrying multiple copies of PBN1 alone show no significant alterations in cell wall glucans or glucan synthase activity, indicating that these effects require the presence of multiple copies of both genes.