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Structural and dynamic basis of acid amido synthetase GH3.1: an investigation of substrate selectivity and major active site access channels.
Mol Biosyst. 2015 Mar; 11(3):809-18.MB

Abstract

Auxin/IAA (Indole-3-acetic acid) plays critical roles in many aspects of plant growth and development. Gretchen Hagen 3.1 (GH3.1) enzyme from grapevine (Vitis vinifera) catalyzes the ATP-dependent conjugation of aspartate to IAA suggesting a significant way to modulate levels of cellular auxins/IAA. It is reported that VvGH3.1 prefers IAA as the substrate than 1-naphthaleneacetic acid (NAA) and benzothiazole-2-oxyacetic acid (BTOA), whereas the detailed interaction mechanism of these substrates remains unclear. In this study, based on the recently reported crystal structure of VvGH3.1 and AtGH3.12, the open form of VvGH3.1 was built. Then combined computational techniques including molecular docking, molecular dynamics (MD) simulations, Molecular Mechanics Generalized Born Surface Area and Poisson-Boltzmann Surface Area (MM-GB/PBSA) methods and active site access channel analysis were utilized to investigate the binding mechanism of three substrates, IAA, NAA and BTOA, and dynamic behaviors of GH3.1 induced by substrate binding. The predicted binding free energy is in agreement with the experimental work with an order of IAA < NAA < BTOA. Key residues interacting with three substrates and residues specifically binding to one of them were identified. The strong hydrogen bond interaction formed between IAA and Ser108, Ser339, Gln560 makes it the best substrate over NAA and BTOA. The dynamic behaviors, especially in the dominant access channels of IAA and NAA bound GH3.1, were found to be different from those in the BTOA-GH3.1 system with larger bottleneck radius and shorter length. This study provided novel insight to understand the substrate selectivity mechanism of GH3.1 and also for the rational design of novel auxin-based herbicides and growth regulators.

Authors+Show Affiliations

Key Lab of Applied Mycology, College of Life Science, Qingdao Agricultural University, Qingdao 266109, China. dujuannx@126.com.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25531425

Citation

Wang, Xue, et al. "Structural and Dynamic Basis of Acid Amido Synthetase GH3.1: an Investigation of Substrate Selectivity and Major Active Site Access Channels." Molecular BioSystems, vol. 11, no. 3, 2015, pp. 809-18.
Wang X, Du J, Yao X. Structural and dynamic basis of acid amido synthetase GH3.1: an investigation of substrate selectivity and major active site access channels. Mol Biosyst. 2015;11(3):809-18.
Wang, X., Du, J., & Yao, X. (2015). Structural and dynamic basis of acid amido synthetase GH3.1: an investigation of substrate selectivity and major active site access channels. Molecular BioSystems, 11(3), 809-18. https://doi.org/10.1039/c4mb00608a
Wang X, Du J, Yao X. Structural and Dynamic Basis of Acid Amido Synthetase GH3.1: an Investigation of Substrate Selectivity and Major Active Site Access Channels. Mol Biosyst. 2015;11(3):809-18. PubMed PMID: 25531425.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Structural and dynamic basis of acid amido synthetase GH3.1: an investigation of substrate selectivity and major active site access channels. AU - Wang,Xue, AU - Du,Juan, AU - Yao,Xiaojun, Y1 - 2014/12/22/ PY - 2014/12/23/entrez PY - 2014/12/23/pubmed PY - 2015/10/22/medline SP - 809 EP - 18 JF - Molecular bioSystems JO - Mol Biosyst VL - 11 IS - 3 N2 - Auxin/IAA (Indole-3-acetic acid) plays critical roles in many aspects of plant growth and development. Gretchen Hagen 3.1 (GH3.1) enzyme from grapevine (Vitis vinifera) catalyzes the ATP-dependent conjugation of aspartate to IAA suggesting a significant way to modulate levels of cellular auxins/IAA. It is reported that VvGH3.1 prefers IAA as the substrate than 1-naphthaleneacetic acid (NAA) and benzothiazole-2-oxyacetic acid (BTOA), whereas the detailed interaction mechanism of these substrates remains unclear. In this study, based on the recently reported crystal structure of VvGH3.1 and AtGH3.12, the open form of VvGH3.1 was built. Then combined computational techniques including molecular docking, molecular dynamics (MD) simulations, Molecular Mechanics Generalized Born Surface Area and Poisson-Boltzmann Surface Area (MM-GB/PBSA) methods and active site access channel analysis were utilized to investigate the binding mechanism of three substrates, IAA, NAA and BTOA, and dynamic behaviors of GH3.1 induced by substrate binding. The predicted binding free energy is in agreement with the experimental work with an order of IAA < NAA < BTOA. Key residues interacting with three substrates and residues specifically binding to one of them were identified. The strong hydrogen bond interaction formed between IAA and Ser108, Ser339, Gln560 makes it the best substrate over NAA and BTOA. The dynamic behaviors, especially in the dominant access channels of IAA and NAA bound GH3.1, were found to be different from those in the BTOA-GH3.1 system with larger bottleneck radius and shorter length. This study provided novel insight to understand the substrate selectivity mechanism of GH3.1 and also for the rational design of novel auxin-based herbicides and growth regulators. SN - 1742-2051 UR - https://www.unboundmedicine.com/medline/citation/25531425/Structural_and_dynamic_basis_of_acid_amido_synthetase_GH3_1:_an_investigation_of_substrate_selectivity_and_major_active_site_access_channels_ L2 - https://doi.org/10.1039/c4mb00608a DB - PRIME DP - Unbound Medicine ER -