Methanol and sorbitol affect the molecular dynamics of arginine deiminase: insights for improving its stability

IF 0.5 4区生物学 Q4 BIOCHEMICAL RESEARCH METHODS Current Proteomics Pub Date : 2022-05-13 DOI:10.2174/1570164619666220513123509

M. Zarei, S. Sabetian, M. Rahbar, M. Negahdaripour

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Abstract

Arginine deiminase enzyme of Mycoplasma arginini (MaADI) is a potential anti-cancer agent for treating arginine-auxotrophic cancers. Investigating the protein stability in the presence of osmolytes can help to increase protein stability under various stressed conditions. In this study, the stability and dynamics of MaADI were investigated in pure water and solutions of 1 M sorbitol, 10% (v/v) methanol, and 50% (v/v) methanol using molecular dynamics simulation. Sorbitol was found to stabilize the protein, whereas high-concentrated methanol destabilized it. Sorbitol molecules interacted with the protein through hydrogen bonding and reduced the protein fluctuations as well. At 50% methanol, the flexibility of regions 4-8, 195-201, 314-324, and 332-337 in the MaADI was increased; whereas residues 195-201 showed the highest variations. Thus, these regions of MaADI, especially 195-201, are the most sensitive regions in the presence of denaturing agents and can be subjected to protein engineering toward improving the stability of MaADI.

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甲醇和山梨醇影响精氨酸脱亚胺酶的分子动力学:提高其稳定性的见解

精氨酸支原体(Mycoplasma arginini, MaADI)的精氨酸脱亚胺酶(Arginine de亚胺酶)是一种治疗精氨酸营养不良癌症的潜在抗癌药物。研究渗透物存在下的蛋白质稳定性有助于提高蛋白质在各种应激条件下的稳定性。本研究通过分子动力学模拟研究了MaADI在纯水和1 M山梨醇、10% (v/v)甲醇和50% (v/v)甲醇溶液中的稳定性和动力学。山梨醇可以稳定蛋白质，而高浓度甲醇则会使其不稳定。山梨醇分子通过氢键与蛋白质相互作用，减少了蛋白质的波动。甲醇浓度为50%时，MaADI中4-8、195-201、314-324和332-337区的柔韧性增加;而残留195 ~ 201的变异最大。因此，MaADI的这些区域，特别是195-201，是变性剂存在时最敏感的区域，可以通过蛋白质工程来提高MaADI的稳定性。

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来源期刊

Current Proteomics BIOCHEMICAL RESEARCH METHODS-BIOCHEMISTRY & MOLECULAR BIOLOGY

CiteScore

1.60

自引率

0.00%

发文量

审稿时长

>0 weeks

期刊介绍： Research in the emerging field of proteomics is growing at an extremely rapid rate. The principal aim of Current Proteomics is to publish well-timed in-depth/mini review articles in this fast-expanding area on topics relevant and significant to the development of proteomics. Current Proteomics is an essential journal for everyone involved in proteomics and related fields in both academia and industry. Current Proteomics publishes in-depth/mini review articles in all aspects of the fast-expanding field of proteomics. All areas of proteomics are covered together with the methodology, software, databases, technological advances and applications of proteomics, including functional proteomics. Diverse technologies covered include but are not limited to: Protein separation and characterization techniques 2-D gel electrophoresis and image analysis Techniques for protein expression profiling including mass spectrometry-based methods and algorithms for correlative database searching Determination of co-translational and post- translational modification of proteins Protein/peptide microarrays Biomolecular interaction analysis Analysis of protein complexes Yeast two-hybrid projects Protein-protein interaction (protein interactome) pathways and cell signaling networks Systems biology Proteome informatics (bioinformatics) Knowledge integration and management tools High-throughput protein structural studies (using mass spectrometry, nuclear magnetic resonance and X-ray crystallography) High-throughput computational methods for protein 3-D structure as well as function determination Robotics, nanotechnology, and microfluidics.