Molecular Dynamics Simulations Study of the Interactions between Human Dipeptidyl-Peptidase III and Two Substrates

Human dipeptidyl-peptidase III (hDPP III) is capable of specifically cleaving dipeptides from the N-terminal of small peptides with biological activity such as angiotensin II (Ang II, DRVYIHPF), and participates in blood pressure regulation, pain modulation, and the development of cancers in human b...

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Autores principales:	Shitao Zhang, Shuai Lv, Xueqi Fu, Lu Han, Weiwei Han, Wannan Li
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	human dipeptidyl-peptidase III substrate molecular dynamics simulations conformational changes Organic chemistry QD241-441
Acceso en línea:	https://doaj.org/article/43ac0afdd4d0422e800774620c72a859
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spelling	oai:doaj.org-article:43ac0afdd4d0422e800774620c72a8592021-11-11T18:29:30ZMolecular Dynamics Simulations Study of the Interactions between Human Dipeptidyl-Peptidase III and Two Substrates10.3390/molecules262164921420-3049https://doaj.org/article/43ac0afdd4d0422e800774620c72a8592021-10-01T00:00:00Zhttps://www.mdpi.com/1420-3049/26/21/6492https://doaj.org/toc/1420-3049Human dipeptidyl-peptidase III (hDPP III) is capable of specifically cleaving dipeptides from the N-terminal of small peptides with biological activity such as angiotensin II (Ang II, DRVYIHPF), and participates in blood pressure regulation, pain modulation, and the development of cancers in human biological activities. In this study, 500 ns molecular dynamics simulations were performed on free-hDPP III (PDB code: 5E33), hDPP III-Ang II (PDB code: 5E2Q), and hDPP III-IVYPW (PDB code: 5E3C) to explore how these two peptides affect the catalytic efficiency of enzymes in terms of the binding mode and the conformational changes. Our results indicate that in the case of the hDPP III-Ang II complex, subsite S1 became small and hydrophobic, which might be propitious for the nucleophile to attack the substrate. The structures of the most stable conformations of the three systems revealed that Arg421-Lys423 could form an α-helix with the presence of Ang II, but only part of the α-helix was produced in hDPP III-IVYPW. As the hinge structure in hDPP III, the conformational changes that took place in the Arg421-Lys423 residue could lead to the changes in the shape and space of the catalytic subsites, which might allow water to function as a nucleophile to attack the substrate. Our results may provide new clues to enable the design of new inhibitors for hDPP III in the future.Shitao ZhangShuai LvXueqi FuLu HanWeiwei HanWannan LiMDPI AGarticlehuman dipeptidyl-peptidase IIIsubstratemolecular dynamics simulationsconformational changesOrganic chemistryQD241-441ENMolecules, Vol 26, Iss 6492, p 6492 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	human dipeptidyl-peptidase III substrate molecular dynamics simulations conformational changes Organic chemistry QD241-441
spellingShingle	human dipeptidyl-peptidase III substrate molecular dynamics simulations conformational changes Organic chemistry QD241-441 Shitao Zhang Shuai Lv Xueqi Fu Lu Han Weiwei Han Wannan Li Molecular Dynamics Simulations Study of the Interactions between Human Dipeptidyl-Peptidase III and Two Substrates
description	Human dipeptidyl-peptidase III (hDPP III) is capable of specifically cleaving dipeptides from the N-terminal of small peptides with biological activity such as angiotensin II (Ang II, DRVYIHPF), and participates in blood pressure regulation, pain modulation, and the development of cancers in human biological activities. In this study, 500 ns molecular dynamics simulations were performed on free-hDPP III (PDB code: 5E33), hDPP III-Ang II (PDB code: 5E2Q), and hDPP III-IVYPW (PDB code: 5E3C) to explore how these two peptides affect the catalytic efficiency of enzymes in terms of the binding mode and the conformational changes. Our results indicate that in the case of the hDPP III-Ang II complex, subsite S1 became small and hydrophobic, which might be propitious for the nucleophile to attack the substrate. The structures of the most stable conformations of the three systems revealed that Arg421-Lys423 could form an α-helix with the presence of Ang II, but only part of the α-helix was produced in hDPP III-IVYPW. As the hinge structure in hDPP III, the conformational changes that took place in the Arg421-Lys423 residue could lead to the changes in the shape and space of the catalytic subsites, which might allow water to function as a nucleophile to attack the substrate. Our results may provide new clues to enable the design of new inhibitors for hDPP III in the future.
format	article
author	Shitao Zhang Shuai Lv Xueqi Fu Lu Han Weiwei Han Wannan Li
author_facet	Shitao Zhang Shuai Lv Xueqi Fu Lu Han Weiwei Han Wannan Li
author_sort	Shitao Zhang
title	Molecular Dynamics Simulations Study of the Interactions between Human Dipeptidyl-Peptidase III and Two Substrates
title_short	Molecular Dynamics Simulations Study of the Interactions between Human Dipeptidyl-Peptidase III and Two Substrates
title_full	Molecular Dynamics Simulations Study of the Interactions between Human Dipeptidyl-Peptidase III and Two Substrates
title_fullStr	Molecular Dynamics Simulations Study of the Interactions between Human Dipeptidyl-Peptidase III and Two Substrates
title_full_unstemmed	Molecular Dynamics Simulations Study of the Interactions between Human Dipeptidyl-Peptidase III and Two Substrates
title_sort	molecular dynamics simulations study of the interactions between human dipeptidyl-peptidase iii and two substrates
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/43ac0afdd4d0422e800774620c72a859
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Molecular Dynamics Simulations Study of the Interactions between Human Dipeptidyl-Peptidase III and Two Substrates

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