The mechanistic role of active site residues in non-stereo haloacid dehalogenase E(DehE)

Dehalogenase E (DehE) is a non-stereospecific enzyme produced by the soil bacterium, Rhizobium sp. RC1. Till now, the catalytic mechanism of DehE remains unclear although several literature concerning its structure and function are available. Since DehE is non-stereospecific, the enzyme was hypothe...

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Main Authors:	Zainal Abidin, Muhammad Hasanuddin, Abd Halim, Khairul Bariyyah, Huyop, Fahrul Zaman, Tengku Abdul Hamid, Tengku Haziyamin, Abdul Wahab, Roswanira, Abdul Hamid, Azzmer Azzar
Format:	Article
Language:	English English English
Published:	Elsevier Ltd 2019
Subjects:	Q Science (General) QD Chemistry
Online Access:	http://irep.iium.edu.my/72292/ http://irep.iium.edu.my/72292/ http://irep.iium.edu.my/72292/ http://irep.iium.edu.my/72292/1/72292_The%20mechanistic%20role%20of%20active%20site%20residues.pdf http://irep.iium.edu.my/72292/7/72292_Journal%20of%20Molecular%20Graphics%20and%20Modelling_scopus.pdf http://irep.iium.edu.my/72292/13/72292_The%20mechanistic%20role%20of%20active%20site%20residues%20in%20non-stereo%20haloacid%20dehalogenase%20E%20%28DehE%29_WOS.pdf

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spelling	iium-722922019-07-31T06:08:18Z http://irep.iium.edu.my/72292/ The mechanistic role of active site residues in non-stereo haloacid dehalogenase E(DehE) Zainal Abidin, Muhammad Hasanuddin Abd Halim, Khairul Bariyyah Huyop, Fahrul Zaman Tengku Abdul Hamid, Tengku Haziyamin Abdul Wahab, Roswanira Abdul Hamid, Azzmer Azzar Q Science (General) QD Chemistry Dehalogenase E (DehE) is a non-stereospecific enzyme produced by the soil bacterium, Rhizobium sp. RC1. Till now, the catalytic mechanism of DehE remains unclear although several literature concerning its structure and function are available. Since DehE is non-stereospecific, the enzyme was hypothesized to follow a ‘direct attack mechanism’ for the catalytic breakdown of a haloacid. For a molecular insight, the DehE modelled structure was docked in silico with the substrate 2-chloropropionic acid (2CP) in the active site. The ideal position of DehE residues that allowed a direct attack mechanism was then assessed via molecular dynamics (MD) simulation. It was revealed that the essential catalytic water was hydrogen bonded to the ‘water-bearer’, Asn114, at a relatively constant distance of ~2.0 Å after 50 ns. The same water molecule was also closely sited to the catalytic Asp189 at an average distance of ~2.0 Å, signifying the imperative role of the latter to initiate proton abstraction for water activation. This reaction was crucial to promote a direct attack on the a-carbon of 2CP to eject the halide ion. The water molecule was oriented favourably towards the a-carbon of 2CP at an angle of ~75�, mirrored by the formation of stable enzyme-substrate orientations throughout the simulation. The data therefore substantiated that the degradation of a haloacid by DehE followed a ‘direct attack mechanism’. Hence, this study offers valuable information into future advancements in the engineering of haloacid dehalogenases with improved activity and selectivity, as well as functionality in solvents other than water. Elsevier Ltd 2019 Article PeerReviewed application/pdf en http://irep.iium.edu.my/72292/1/72292_The%20mechanistic%20role%20of%20active%20site%20residues.pdf application/pdf en http://irep.iium.edu.my/72292/7/72292_Journal%20of%20Molecular%20Graphics%20and%20Modelling_scopus.pdf application/pdf en http://irep.iium.edu.my/72292/13/72292_The%20mechanistic%20role%20of%20active%20site%20residues%20in%20non-stereo%20haloacid%20dehalogenase%20E%20%28DehE%29_WOS.pdf Zainal Abidin, Muhammad Hasanuddin and Abd Halim, Khairul Bariyyah and Huyop, Fahrul Zaman and Tengku Abdul Hamid, Tengku Haziyamin and Abdul Wahab, Roswanira and Abdul Hamid, Azzmer Azzar (2019) The mechanistic role of active site residues in non-stereo haloacid dehalogenase E(DehE). Journal of Molecular Graphics and Modelling, 90. pp. 219-225. ISSN 1093-3263 https://www.sciencedirect.com/science/article/pii/S1093326318308714?via%3Dihub https://doi.org/10.1016/j.jmgm.2019.05.003
repository_type	Digital Repository
institution_category	Local University
institution	International Islamic University Malaysia
building	IIUM Repository
collection	Online Access
language	English English English
topic	Q Science (General) QD Chemistry
spellingShingle	Q Science (General) QD Chemistry Zainal Abidin, Muhammad Hasanuddin Abd Halim, Khairul Bariyyah Huyop, Fahrul Zaman Tengku Abdul Hamid, Tengku Haziyamin Abdul Wahab, Roswanira Abdul Hamid, Azzmer Azzar The mechanistic role of active site residues in non-stereo haloacid dehalogenase E(DehE)
description	Dehalogenase E (DehE) is a non-stereospecific enzyme produced by the soil bacterium, Rhizobium sp. RC1. Till now, the catalytic mechanism of DehE remains unclear although several literature concerning its structure and function are available. Since DehE is non-stereospecific, the enzyme was hypothesized to follow a ‘direct attack mechanism’ for the catalytic breakdown of a haloacid. For a molecular insight, the DehE modelled structure was docked in silico with the substrate 2-chloropropionic acid (2CP) in the active site. The ideal position of DehE residues that allowed a direct attack mechanism was then assessed via molecular dynamics (MD) simulation. It was revealed that the essential catalytic water was hydrogen bonded to the ‘water-bearer’, Asn114, at a relatively constant distance of ~2.0 Å after 50 ns. The same water molecule was also closely sited to the catalytic Asp189 at an average distance of ~2.0 Å, signifying the imperative role of the latter to initiate proton abstraction for water activation. This reaction was crucial to promote a direct attack on the a-carbon of 2CP to eject the halide ion. The water molecule was oriented favourably towards the a-carbon of 2CP at an angle of ~75�, mirrored by the formation of stable enzyme-substrate orientations throughout the simulation. The data therefore substantiated that the degradation of a haloacid by DehE followed a ‘direct attack mechanism’. Hence, this study offers valuable information into future advancements in the engineering of haloacid dehalogenases with improved activity and selectivity, as well as functionality in solvents other than water.
format	Article
author	Zainal Abidin, Muhammad Hasanuddin Abd Halim, Khairul Bariyyah Huyop, Fahrul Zaman Tengku Abdul Hamid, Tengku Haziyamin Abdul Wahab, Roswanira Abdul Hamid, Azzmer Azzar
author_facet	Zainal Abidin, Muhammad Hasanuddin Abd Halim, Khairul Bariyyah Huyop, Fahrul Zaman Tengku Abdul Hamid, Tengku Haziyamin Abdul Wahab, Roswanira Abdul Hamid, Azzmer Azzar
author_sort	Zainal Abidin, Muhammad Hasanuddin
title	The mechanistic role of active site residues in non-stereo haloacid dehalogenase E(DehE)
title_short	The mechanistic role of active site residues in non-stereo haloacid dehalogenase E(DehE)
title_full	The mechanistic role of active site residues in non-stereo haloacid dehalogenase E(DehE)
title_fullStr	The mechanistic role of active site residues in non-stereo haloacid dehalogenase E(DehE)
title_full_unstemmed	The mechanistic role of active site residues in non-stereo haloacid dehalogenase E(DehE)
title_sort	mechanistic role of active site residues in non-stereo haloacid dehalogenase e(dehe)
publisher	Elsevier Ltd
publishDate	2019
url	http://irep.iium.edu.my/72292/ http://irep.iium.edu.my/72292/ http://irep.iium.edu.my/72292/ http://irep.iium.edu.my/72292/1/72292_The%20mechanistic%20role%20of%20active%20site%20residues.pdf http://irep.iium.edu.my/72292/7/72292_Journal%20of%20Molecular%20Graphics%20and%20Modelling_scopus.pdf http://irep.iium.edu.my/72292/13/72292_The%20mechanistic%20role%20of%20active%20site%20residues%20in%20non-stereo%20haloacid%20dehalogenase%20E%20%28DehE%29_WOS.pdf
first_indexed	2023-09-18T21:42:25Z
last_indexed	2023-09-18T21:42:25Z
_version_	1777413228258656256

The mechanistic role of active site residues in non-stereo haloacid dehalogenase E(DehE)

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