PKG Substrate
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PKG Substrate

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PKG Substrate is a selective substrate for cGMP-dependent protein kinase (PKG).

Category
Peptide Inhibitors
Catalog number
BAT-010593
CAS number
81187-14-6
Molecular Formula
C35H67N17O11
Molecular Weight
902.01
PKG Substrate
IUPAC Name
(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-6-amino-2-[[(2S)-2-amino-5-(diaminomethylideneamino)pentanoyl]amino]hexanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-3-hydroxypropanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]propanoyl]amino]pentanedioic acid
Synonyms
Arg-Lys-Arg-Ser-Arg-Ala-Glu; L-arginyl-L-lysyl-L-arginyl-L-seryl-L-arginyl-L-alanyl-L-glutamic acid; N5-(Diaminomethylidene)-L-ornithyl-L-lysyl-N5-(diaminomethylidene)-L-ornithyl-L-seryl-N5-(diaminomethylidene)-L-ornithyl-L-alanyl-L-glutamic acid; (S)-2-((6S,9S,12S,15S,18S,21S)-1,6-diamino-9-(4-aminobutyl)-12,18-bis(3-guanidinopropyl)-15-(hydroxymethyl)-1-imino-21-methyl-7,10,13,16,19-pentaoxo-2,8,11,14,17,20-hexaazadocosanamido)pentanedioic acid
Appearance
White Lyophilized Powder
Purity
≥95%
Density
1.6±0.1 g/cm3
Sequence
RKRSRAE
Storage
Store at -20°C
Solubility
Soluble in Water
InChI
InChI=1S/C35H67N17O11/c1-18(26(56)51-23(32(62)63)11-12-25(54)55)47-28(58)21(9-5-15-45-34(40)41)50-31(61)24(17-53)52-30(60)22(10-6-16-46-35(42)43)49-29(59)20(8-2-3-13-36)48-27(57)19(37)7-4-14-44-33(38)39/h18-24,53H,2-17,36-37H2,1H3,(H,47,58)(H,48,57)(H,49,59)(H,50,61)(H,51,56)(H,52,60)(H,54,55)(H,62,63)(H4,38,39,44)(H4,40,41,45)(H4,42,43,46)/t18-,19-,20-,21-,22-,23-,24-/m0/s1
InChI Key
BVKSYBQAXBWINI-LQDRYOBXSA-N
Canonical SMILES
CC(C(=O)NC(CCC(=O)O)C(=O)O)NC(=O)C(CCCN=C(N)N)NC(=O)C(CO)NC(=O)C(CCCN=C(N)N)NC(=O)C(CCCCN)NC(=O)C(CCCN=C(N)N)N
1. cGMP-binding prepares PKG for substrate binding by disclosing the C-terminal domain
Vera Alverdi, Cees Versluis, Arjen Scholten, Gennaro Esposito, Albert J R Heck, Wieger Hemrika, Hortense Mazon, Robert van den Heuvel J Mol Biol . 2008 Feb 1;375(5):1380-93. doi: 10.1016/j.jmb.2007.11.053.
Type I cyclic guanosine 3',5'-monophosphate (cGMP)-dependent protein kinase (PKG) is involved in the nitric oxide/cGMP signaling pathway. PKG has been identified in many different species, ranging from unicelölular organisms to mammals. The enzyme serves as one of the major receptor proteins for intracellular cGMP and controls a variety of cellular responses, ranging from smooth-muscle relaxation to neuronal synaptic plasticity. In the absence of a crystal structure, the three-dimensional structure of the homodimeric 152-kDa kinase PKG is unknown; however, there is evidence that the kinase adopts a distinct cGMP-dependent active conformation when compared to the inactive conformation. We performed mass-spectrometry-based hydrogen/deuterium exchange experiments to obtain detailed information on the structural changes in PKG I alpha induced by cGMP activation. Site-specific exchange measurements confirmed that the autoinhibitory domain and the hinge region become more solvent exposed, whereas the cGMP-binding domains become more protected in holo-PKG (dimeric PKG saturated with four cGMP molecules bound). More surprisingly, our data revealed a specific disclosure of the substrate-binding region of holo-PKG, shedding new light into the kinase-activation process of PKG.
2. The Role of NO/sGC/cGMP/PKG Signaling Pathway in Regulation of Platelet Function
Stepan Gambaryan Cells . 2022 Nov 21;11(22):3704. doi: 10.3390/cells11223704.
Circulating blood platelets are controlled by stimulatory and inhibitory factors, and a tightly regulated equilibrium between these two opposing processes is essential for normal platelet and vascular function. NO/cGMP/ Protein Kinase G (PKG) pathways play a highly significant role in platelet inhibition, which is supported by a large body of studies and data. This review focused on inconsistent and controversial data of NO/sGC/cGMP/PKG signaling in platelets including sources of NO that activate sGC in platelets, the role of sGC/PKG in platelet inhibition/activation, and the complexity of the regulation of platelet inhibitory mechanisms by cGMP/PKG pathways. In conclusion, we suggest that the recently developed quantitative phosphoproteomic method will be a powerful tool for the analysis of PKG-mediated effects. Analysis of phosphoproteins in PKG-activated platelets will reveal many new PKG substrates. A future detailed analysis of these substrates and their involvement in different platelet inhibitory pathways could be a basis for the development of new antiplatelet drugs that may target only specific aspects of platelet functions.
3. Scutellarin's Cardiovascular Endothelium Protective Mechanism: Important Role of PKG-Iα
Lu Li, Chen Chen, Dongmei Zhang, Yang Li, Jian Yang, Jiaxun Li, Lin Li, Weimin Yang, Tao Guo, Na Hu, Xuan Liu PLoS One . 2015 Oct 6;10(10):e0139570. doi: 10.1371/journal.pone.0139570.
Scutellarin (SCU), a flavonoid glycoside compound, has been successfully used in clinic for treatment of ischemic diseases in China. In this report, we checked the effects of SCU on endothelium dysfunction (ED) of coronary artery (CA) against myocardial ischemia reperfusion (MIR) injury in vivo. The involvement of PKG-Iα was further studied using cultured endothelial cells subjected to hypoxia reoxygenation (HR) injury in vitro. In rat MIR model, SCU (45 and 90 mg/kg, iv) significantly reduced ischemic size and restored the endothelium-dependent vasodilation of isolated CA rings. PKG inhibitor Rp-8-Br-cGMP (50 μg/kg, iv) could ameliorate the protective effects of SCU. Increase in phosphorylation of vasodilator-stimulated phosphoprotein (VASP), a main substrate of PKG, at Ser 239 was observed in both heart tissue and serum of SCU-treated animals. In cultured human cardiac microvascular endothelial cells (HCMECs), SCU (1 and 10 μM) dose-dependently protected cell viability and increased the mRNA and protein level of PKG-Iα against HR injury. The activity of PKG was also increased by SCU treatment. The activation of PKG-1α was then studied using targeted proteomic analysis (MRM-MS) checking the phosphorylation state of the autophosphorylation domain (aa42-94). Significant decrease in phosphorylation of PKG-Iα at Ser50, Ser72, Ser89 was induced by HR injury while SCU treatment significantly increased the phosphorylation of PKG-Iα, not only at Ser50, Ser72 and Ser89, but also at Ser44 and Thr58 (two novel phosphorylation domains). Our results demonstrate PKG-Iα might play an important role in the protective effects of SCU on ED against MIR injury.
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