In Silico Functional Characterization of a Hypothetical Protein From Reveals a Novel -Adenosylmethionine-Dependent Methyltransferase Activity
Genomes may now be sequenced in a matter of weeks, leading to an influx of “hypothetical” proteins (HP) whose activities remain a mystery in GenBank. The information included inside these genes has quickly grown in prominence. Thus, we selected to look closely at the structure and function of an HP...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
SAGE Publishing
2023-06-01
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| Series: | Bioinformatics and Biology Insights |
| Online Access: | https://doi.org/10.1177/11779322231184024 |
| _version_ | 1797788772922818560 |
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| author | Md. Habib Ullah Masum Sultana Rajia Uditi Paul Bristi Mir Salma Akter Mohammad Ruhul Amin Tushar Ahmed Shishir Jannatul Ferdous Firoz Ahmed Md. Mizanur Rahaman Otun Saha |
| author_facet | Md. Habib Ullah Masum Sultana Rajia Uditi Paul Bristi Mir Salma Akter Mohammad Ruhul Amin Tushar Ahmed Shishir Jannatul Ferdous Firoz Ahmed Md. Mizanur Rahaman Otun Saha |
| author_sort | Md. Habib Ullah Masum |
| collection | DOAJ |
| description | Genomes may now be sequenced in a matter of weeks, leading to an influx of “hypothetical” proteins (HP) whose activities remain a mystery in GenBank. The information included inside these genes has quickly grown in prominence. Thus, we selected to look closely at the structure and function of an HP (AFF25514.1; 246 residues) from Pasteurella multocida (PM) subsp. multocida str. HN06. Possible insights into bacterial adaptation to new environments and metabolic changes might be gained by studying the functions of this protein. The PM HN06 2293 gene encodes an alkaline cytoplasmic protein with a molecular weight of 28352.60 Da, an isoelectric point (pI) of 9.18, and an overall average hydropathicity of around −0.565. One of its functional domains, tRNA (adenine (37)-N6)-methyltransferase TrmO, is a S -adenosylmethionine (SAM)-dependent methyltransferase (MTase), suggesting that it belongs to the Class VIII SAM-dependent MTase family. The tertiary structures represented by HHpred and I-TASSER models were found to be flawless. We predicted the model’s active site using the Computed Atlas of Surface Topography of Proteins (CASTp) and FTSite servers, and then displayed it in 3 dimensional (3D) using PyMOL and BIOVIA Discovery Studio. Based on molecular docking (MD) results, we know that HP interacts with SAM and S -adenosylhomocysteine (SAH), 2 crucial metabolites in the tRNA methylation process, with binding affinities of 7.4 and 7.5 kcal/mol, respectively. Molecular dynamic simulations (MDS) of the docked complex, which included only modest structural adjustments, corroborated the strong binding affinity of SAM and SAH to the HP. Evidence for HP’s possible role as an SAM-dependent MTase was therefore given by the findings of Multiple sequence alignment (MSA), MD, and molecular dynamic modeling. These in silico data suggest that the investigated HP might be used as a useful adjunct in the investigation of Pasteurella infections and the development of drugs to treat zoonotic pasteurellosis. |
| first_indexed | 2024-03-13T01:40:19Z |
| format | Article |
| id | doaj.art-fac915d62a3040588b3f68f7320ce1c5 |
| institution | Directory Open Access Journal |
| issn | 1177-9322 |
| language | English |
| last_indexed | 2024-03-13T01:40:19Z |
| publishDate | 2023-06-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Bioinformatics and Biology Insights |
| spelling | doaj.art-fac915d62a3040588b3f68f7320ce1c52023-07-03T14:34:18ZengSAGE PublishingBioinformatics and Biology Insights1177-93222023-06-011710.1177/11779322231184024In Silico Functional Characterization of a Hypothetical Protein From Reveals a Novel -Adenosylmethionine-Dependent Methyltransferase ActivityMd. Habib Ullah Masum0Sultana Rajia1Uditi Paul Bristi2Mir Salma Akter3Mohammad Ruhul Amin4Tushar Ahmed Shishir5Jannatul Ferdous6Firoz Ahmed7Md. Mizanur Rahaman8Otun Saha9Department of Microbiology, Noakhali Science and Technology University, Noakhali, BangladeshDepartment of Microbiology, Noakhali Science and Technology University, Noakhali, BangladeshDepartment of Microbiology, Noakhali Science and Technology University, Noakhali, BangladeshDepartment of Microbiology, Noakhali Science and Technology University, Noakhali, BangladeshDepartment of Microbiology, Noakhali Science and Technology University, Noakhali, BangladeshDepartment of Mathematics and Natural Sciences, BRAC University, Dhaka, BangladeshDepartment of Medicine, Abdul Malek Ukil Medical College, Noakhali, BangladeshDepartment of Microbiology, Noakhali Science and Technology University, Noakhali, BangladeshDepartment of Microbiology, University of Dhaka, Dhaka, BangladeshDepartment of Microbiology, Noakhali Science and Technology University, Noakhali, BangladeshGenomes may now be sequenced in a matter of weeks, leading to an influx of “hypothetical” proteins (HP) whose activities remain a mystery in GenBank. The information included inside these genes has quickly grown in prominence. Thus, we selected to look closely at the structure and function of an HP (AFF25514.1; 246 residues) from Pasteurella multocida (PM) subsp. multocida str. HN06. Possible insights into bacterial adaptation to new environments and metabolic changes might be gained by studying the functions of this protein. The PM HN06 2293 gene encodes an alkaline cytoplasmic protein with a molecular weight of 28352.60 Da, an isoelectric point (pI) of 9.18, and an overall average hydropathicity of around −0.565. One of its functional domains, tRNA (adenine (37)-N6)-methyltransferase TrmO, is a S -adenosylmethionine (SAM)-dependent methyltransferase (MTase), suggesting that it belongs to the Class VIII SAM-dependent MTase family. The tertiary structures represented by HHpred and I-TASSER models were found to be flawless. We predicted the model’s active site using the Computed Atlas of Surface Topography of Proteins (CASTp) and FTSite servers, and then displayed it in 3 dimensional (3D) using PyMOL and BIOVIA Discovery Studio. Based on molecular docking (MD) results, we know that HP interacts with SAM and S -adenosylhomocysteine (SAH), 2 crucial metabolites in the tRNA methylation process, with binding affinities of 7.4 and 7.5 kcal/mol, respectively. Molecular dynamic simulations (MDS) of the docked complex, which included only modest structural adjustments, corroborated the strong binding affinity of SAM and SAH to the HP. Evidence for HP’s possible role as an SAM-dependent MTase was therefore given by the findings of Multiple sequence alignment (MSA), MD, and molecular dynamic modeling. These in silico data suggest that the investigated HP might be used as a useful adjunct in the investigation of Pasteurella infections and the development of drugs to treat zoonotic pasteurellosis.https://doi.org/10.1177/11779322231184024 |
| spellingShingle | Md. Habib Ullah Masum Sultana Rajia Uditi Paul Bristi Mir Salma Akter Mohammad Ruhul Amin Tushar Ahmed Shishir Jannatul Ferdous Firoz Ahmed Md. Mizanur Rahaman Otun Saha In Silico Functional Characterization of a Hypothetical Protein From Reveals a Novel -Adenosylmethionine-Dependent Methyltransferase Activity Bioinformatics and Biology Insights |
| title | In Silico Functional Characterization of a Hypothetical Protein From Reveals a Novel -Adenosylmethionine-Dependent Methyltransferase Activity |
| title_full | In Silico Functional Characterization of a Hypothetical Protein From Reveals a Novel -Adenosylmethionine-Dependent Methyltransferase Activity |
| title_fullStr | In Silico Functional Characterization of a Hypothetical Protein From Reveals a Novel -Adenosylmethionine-Dependent Methyltransferase Activity |
| title_full_unstemmed | In Silico Functional Characterization of a Hypothetical Protein From Reveals a Novel -Adenosylmethionine-Dependent Methyltransferase Activity |
| title_short | In Silico Functional Characterization of a Hypothetical Protein From Reveals a Novel -Adenosylmethionine-Dependent Methyltransferase Activity |
| title_sort | in silico functional characterization of a hypothetical protein from reveals a novel adenosylmethionine dependent methyltransferase activity |
| url | https://doi.org/10.1177/11779322231184024 |
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