Nucleotides Acting at P2Y Receptors: Connecting Structure and Function
文献类型：期刊论文
| 作者 | Jacobson, Kenneth A.2; Paoletta, Silvia2; Katritch, Vsevolod3; Wu, Beili1 ; Gao, Zhan-Guo2; Zhao, Qiang1; Stevens, Raymond C.3; Kiselev, Evgeny2
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| 刊名 | MOLECULAR PHARMACOLOGY
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| 出版日期 | 2015-08 |
| 卷号 | 88期号:2页码:220-230 |
| ISSN号 | 0026-895X |
| DOI | 10.1124/mol.114.095711 |
| 文献子类 | Review |
| 英文摘要 | Eight G protein-coupled P2Y receptor (P2YR) subtypes are important physiologic mediators. The human P2YRs are fully activated by ATP (P2Y(2) and P2Y(11)), ADP (P2Y(1), P2Y(12), and P2Y(13)), UTP (P2Y(2) and P2Y(4)), UDP (P2Y(6) and P2Y(14)), and UDP glucose (P2Y(14)). Their structural elucidation is progressing rapidly. The X-ray structures of three ligand complexes of the G(i)-coupled P2Y(12)R and two of the G(q)-coupled P2Y(1)Rs were recently determined and will be especially useful in structure-based ligand design at two P2YR subfamilies. These high-resolution structures, which display unusual binding site features, complement mutagenesis studies for probing ligand recognition and activation. The structural requirements for nucleotide agonist recognition at P2YRs are relatively permissive with respect to the length of the phosphate moiety, but less so with respect to base recognition. Nucleotide-like antagonists and partial agonists are also known for P2Y(1), P2Y(2), P2Y(4), and P2Y(12)Rs. Each P2YR subtype has the ability to be activated by structurally bifunctional agonists, such as dinucleotides, typically, dinucleoside triphosphates or tetraphosphates, and nucleoside polyphosphate sugars (e.g., UDP glucose) as well as the more conventional mononucleotide agonists. A range of dinucleoside polyphosphates, from triphosphates to higher homologs, occurs naturally. Earlier modeling predictions of the P2YRs were not very accurate, but recent findings have provided much detailed structural insight into this receptor family to aid in the rational design of new drugs. |
| WOS关键词 | HUMAN P2Y(12) RECEPTOR ; URIDINE ADENOSINE-TETRAPHOSPHATE ; DINUCLEOSIDE POLYPHOSPHATES ; PLATELET-AGGREGATION ; ADP RECEPTOR ; DIADENOSINE POLYPHOSPHATES ; MUTATIONAL ANALYSIS ; URACIL NUCLEOTIDES ; SELECTIVE AGONISTS ; CYSTIC-FIBROSIS |
| 资助项目 | NIGMS NIH HHS[U54 GM094618] ; NIDDK NIH HHS[Z01 DK031126] ; NIDDK NIH HHS[Z01-DK031126-08] ; Intramural NIH HHS[ZIA DK031116-27] |
| WOS研究方向 | Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:000357092600001 |
| 出版者 | AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/276462]  |
| 专题 | 药物靶标结构与功能中心 |
| 通讯作者 | Jacobson, Kenneth A. |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Mat Med, Key Lab Receptor Res, Shanghai 200031, Peoples R China 2.NIDDK, Mol Recognit Sect, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA; 3.Univ So Calif, Dana & David Dornsife Sch Letters Arts & Sci, Bridge Inst, Los Angeles, CA USA; |
| 推荐引用方式 GB/T 7714 | Jacobson, Kenneth A.,Paoletta, Silvia,Katritch, Vsevolod,et al. Nucleotides Acting at P2Y Receptors: Connecting Structure and Function[J]. MOLECULAR PHARMACOLOGY,2015,88(2):220-230. |
| APA | Jacobson, Kenneth A..,Paoletta, Silvia.,Katritch, Vsevolod.,Wu, Beili.,Gao, Zhan-Guo.,...&Kiselev, Evgeny.(2015).Nucleotides Acting at P2Y Receptors: Connecting Structure and Function.MOLECULAR PHARMACOLOGY,88(2),220-230. |
| MLA | Jacobson, Kenneth A.,et al."Nucleotides Acting at P2Y Receptors: Connecting Structure and Function".MOLECULAR PHARMACOLOGY 88.2(2015):220-230. |
入库方式： OAI收割
来源：上海药物研究所
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