干旱区生态环境知识资源中心(Arid): Conformational analysis of a cyclic AKH neuropeptide analog that elicits selective activity on locust versus honeybee receptor

Arid

DOI	10.1016/j.ibmb.2020.103362
	Conformational analysis of a cyclic AKH neuropeptide analog that elicits selective activity on locust versus honeybee receptor
	Abdulganiyyu, Ibrahim A.; Kaczmarek, Krzysztof; Zabrocki, Janusz; Nachman, Ronald J.; Marchal, Elisabeth; Schellens, Sam; Verlinden, Heleen; Vanden Broeck, Jozef; Marco, Heather; Jackson, Graham E.
通讯作者	Jackson, GE
来源期刊	INSECT BIOCHEMISTRY AND MOLECULAR BIOLOGY
ISSN	0965-1748
EISSN	1879-0240
出版年	2020
卷号	125
英文摘要	Neuropeptides belonging to the adipokinetic hormone (AKH) family elicit metabolic effects as their main function in insects, by mobilizing trehalose, diacylgycerol, or proline, which are released from the fat body into the hemolymph as energy sources for muscle contraction required for energy-intensive processes, such as locomotion. One of the AKHs produced in locusts is a decapeptide, Locmi-AKH-I (pELNFTPNWGT-NH2). A head-totail cyclic, octapeptide analog of Locmi-AKH-I, cycloAKH (cyclo[LNFTPNWG]) was synthesized to severely restrict the conformational freedom of the AKH structure. In vitro, cycloAKH selectively retains full efficacy on a pest insect (desert locust) AKH receptor, while showing little or no activation of the AKH receptor of a beneficial insect (honeybee). Molecular dynamic analysis incorporating NMR data indicate that cycloAKH preferentially adopts a type II beta-turn under micelle conditions, whereas its linear counterpart and natural AKH adopts a type VI beta-turn under similar conditions. CycloAKH, linear LNFTPNWG-NH2, and Locmi-AKH-I feature the same binding site during docking simulations with the desert locust AKH receptor (Schgr-AKHR), but differ in the details of the ligand/receptor interactions. However, cycloAKH failed to enter the binding pocket of the honeybee receptor 3D model during docking simulations. Since the locust AKH receptor has a greater tolerance than the honeybee receptor for the cyclic conformational constraint in vitro receptor assays, it could suggest a greater tolerance for a shift in the direction of the type II beta turn exhibited by cycloAKH from the type VI beta turn of the linear octapeptide and the native locust decapeptide AKH. Selectivity in biostable mimetic analogs could potentially be enhanced by incorporating conformational constraints that emphasize this shift. Biostable mimetic analogs of AKH offer the potential of selectively disrupting AKH-regulated processes, leading to novel, environmentally benign control strategies for pest insect populations.
英文关键词	Conformational restriction Agonist Insect control NMR Molecular dynamics
类型	Article
语种	英语
开放获取类型	Green Accepted
收录类别	SCI-E
WOS记录号	WOS:000572388600003
WOS关键词	NUCLEAR-MAGNETIC-RESONANCE ; PROTEIN-COUPLED RECEPTORS ; CIS-PEPTIDE BOND ; IDENTIFIES OPTIMAL STEREOCHEMISTRY ; PIGMENT-CONCENTRATING HORMONE ; TERMINAL STRUCTURAL MOTIF ; INSECT KININ ANALOGS ; ADIPOKINETIC HORMONES ; CHEMICAL-SHIFTS ; WATER SUPPRESSION
WOS类目	Biochemistry & Molecular Biology ; Entomology
WOS研究方向	Biochemistry & Molecular Biology ; Entomology
资源类型	期刊论文
条目标识符	http://119.78.100.177/qdio/handle/2XILL650/326476
作者单位	[Abdulganiyyu, Ibrahim A.; Jackson, Graham E.] Univ Cape Town, Dept Chem, ZA-7701 Cape Town, South Africa; [Marco, Heather] Univ Cape Town, Biol Sci, ZA-7701 Cape Town, South Africa; [Kaczmarek, Krzysztof; Zabrocki, Janusz; Nachman, Ronald J.] USDA, Insect Control & Cotton Dis Res Unit, Southern Plains Agr Res Ctr, 2881 F-B Rd, College Stn, TX 77845 USA; [Kaczmarek, Krzysztof; Zabrocki, Janusz] Lodz Univ Technol, PL-90924 Lodz, Poland; [Marchal, Elisabeth; Schellens, Sam; Verlinden, Heleen; Vanden Broeck, Jozef] Katholieke Univ Leuven, Mol Dev Physiol & Signal Transduct, Naamsestr 59, B-3000 Leuven, Belgium
推荐引用方式 GB/T 7714	Abdulganiyyu, Ibrahim A.,Kaczmarek, Krzysztof,Zabrocki, Janusz,et al. Conformational analysis of a cyclic AKH neuropeptide analog that elicits selective activity on locust versus honeybee receptor[J],2020,125.
APA	Abdulganiyyu, Ibrahim A..,Kaczmarek, Krzysztof.,Zabrocki, Janusz.,Nachman, Ronald J..,Marchal, Elisabeth.,...&Jackson, Graham E..(2020).Conformational analysis of a cyclic AKH neuropeptide analog that elicits selective activity on locust versus honeybee receptor.INSECT BIOCHEMISTRY AND MOLECULAR BIOLOGY,125.
MLA	Abdulganiyyu, Ibrahim A.,et al."Conformational analysis of a cyclic AKH neuropeptide analog that elicits selective activity on locust versus honeybee receptor".INSECT BIOCHEMISTRY AND MOLECULAR BIOLOGY 125(2020).