Structure prediction and functional analyses of a thermostable lipase obtained from <i>Shewanella putrefaciens</i>

Khan, Faez Iqbal; Nizami, Bilal; Anwer, Razique; Gu, Kai; Bisetty, Krishna; Hassan, Md. Imtaiyaz; Wei, Dong‐Qing

doi:10.1080/07391102.2016.1206837

Cited by 36 publications

(21 citation statements)

References 64 publications

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“…Next to selectivity and activity, thermostability is one of the most desirable traits of lipases (Dizge et al, 2009; Avila-Cisneros et al, 2014; Khan et al, 2016). Several factors define this property such as the number of hydrogen bonds, salt bridges, stabilization of secondary structures, occurrence of disulfide bonds, higher number of proline residues, higher polar surface area, shortening of loops, and stabilization of the lid domain (Pack and Yoo, 2004; Santarossa et al, 2005; Zhou et al, 2008; Khan et al, 2015a,b).…”

Section: Effects On Thermostabilitymentioning

confidence: 99%

The Lid Domain in Lipases: Structural and Functional Determinant of Enzymatic Properties

Khan

Lan

Durrani

et al. 2017

Front. Bioeng. Biotechnol.

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Lipases are important industrial enzymes. Most of the lipases operate at lipid–water interfaces enabled by a mobile lid domain located over the active site. Lid protects the active site and hence responsible for catalytic activity. In pure aqueous media, the lid is predominantly closed, whereas in the presence of a hydrophobic layer, it is partially opened. Hence, the lid controls the enzyme activity. In the present review, we have classified lipases into different groups based on the structure of lid domains. It has been observed that thermostable lipases contain larger lid domains with two or more helices, whereas mesophilic lipases tend to have smaller lids in the form of a loop or a helix. Recent developments in lipase engineering addressing the lid regions are critically reviewed here. After on, the dramatic changes in substrate selectivity, activity, and thermostability have been reported. Furthermore, improved computational models can now rationalize these observations by relating it to the mobility of the lid domain. In this contribution, we summarized and critically evaluated the most recent developments in experimental and computational research on lipase lids.

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Section: Effects On Thermostabilitymentioning

confidence: 99%

The Lid Domain in Lipases: Structural and Functional Determinant of Enzymatic Properties

Khan

Lan

Durrani

et al. 2017

Front. Bioeng. Biotechnol.

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280

225

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“…The sequencing were performed with PSI-BLAST [25] and HMMER [26]. Homology modelling was done to predict three dimensional structure of TmPLB1 using (PDB ID: 1FJ2) as the template [27][28][29]. The structure alignment were attained with fold recognition and applied to develop 3D model by Modeler 9.10 [27,30].…”

Section: Protein Sequence and Structure Analysismentioning

confidence: 99%

A Thermolabile Phospholipase B from Talaromyces marneffei GD-0079: Biochemical Characterization and Structure Dynamics Study

et al. 2020

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Phospholipase B (EC 3.1.1.5) are a distinctive group of enzymes that catalyzes the hydrolysis of fatty acids esterified at the sn-1 and sn-2 positions forming free fatty acids and lysophospholipids. The structural information and catalytic mechanism of phospholipase B are still not clear. Herein, we reported a putative phospholipase B (TmPLB1) from Talaromyces marneffei GD-0079 synthesized by genome mining library. The gene (TmPlb1) was expressed and the TmPLB1 was purified using E. coli shuffle T7 expression system. The putative TmPLB1 was purified by affinity chromatography with a yield of 13.5%. The TmPLB1 showed optimum activity at 35 °C and pH 7.0. The TmPLB1 showed enzymatic activity using Lecithin (soybean > 98% pure), and the hydrolysis of TmPLB1 by 31P NMR showed phosphatidylcholine (PC) as a major phospholipid along with lyso-phospholipids (1-LPC and 2-LPC) and some minor phospholipids. The molecular modeling studies indicate that its active site pocket contains Ser125, Asp183 and His215 as the catalytic triad. The structure dynamics and simulations results explained the conformational changes associated with different environmental conditions. This is the first report on biochemical characterization and structure dynamics of TmPLB1 enzyme. The present study could be helpful to utilize TmPLB1 in food industry for the determination of food components containing phosphorus. Additionally, such enzyme could also be useful in Industry for the modifications of phospholipids.

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“…The plots of the 3D models were readied utilising PyMol and VMD (Visual Molecular Dynamics) 56 . The details of MD simulation method were previously described [57][58][59][60][61] .…”

Section: Molecular Dynamics Simulationmentioning

confidence: 99%

Identifying novel sphingosine kinase 1 inhibitors as therapeutics against breast cancer

Khan

Lai

Anwer

et al. 2019

Journal of Enzyme Inhibition and Medicinal Chemistry

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Sphingosine kinase 1 (SphK1) is a promising therapeutic target against several diseases including mammary cancer. The aim of present work is to identify a potent lead compound against breast cancer using ligand-based virtual screening, molecular docking, MD simulations, and the MMPBSA calculations. The LBVS in molecular and virtual libraries yielded 20,800 hits, which were reduced to 621 by several parameters of drug-likeness, lead-likeness, and PAINS. Furthermore, 55 compounds were selected by ADMET descriptors carried forward for molecular interaction studies with SphK1. The binding energy (DG) of three screened compounds namely ZINC06823429 (-11.36 kcal/mol), ZINC95421501 (-11.29 kcal/mol), and ZINC95421070 (-11.26 kcal/mol) exhibited stronger than standard drug PF-543 (-9.9 kcal/mol). Finally, it was observed that the ZINC06823429 binds tightly to catalytic site of SphK1 and remain stable during MD simulations. This study provides a significant understanding of SphK1 inhibitors that can be used in the development of potential therapeutics against breast cancer.

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Structure prediction and functional analyses of a thermostable lipase obtained from Shewanella putrefaciens

Cited by 36 publications

References 64 publications

The Lid Domain in Lipases: Structural and Functional Determinant of Enzymatic Properties

The Lid Domain in Lipases: Structural and Functional Determinant of Enzymatic Properties

A Thermolabile Phospholipase B from Talaromyces marneffei GD-0079: Biochemical Characterization and Structure Dynamics Study

Identifying novel sphingosine kinase 1 inhibitors as therapeutics against breast cancer

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