Molecular Characterization of Legionellosis Drug Target Candidate Enzyme Phosphoglucosamine Mutase from (strain Paris): An Approach
The harshness of legionellosis differs from mild Pontiac fever to potentially fatal Legionnaire's disease. The increasing development of drug resistance against legionellosis has led to explore new novel drug targets. It has been found that phosphoglucosamine mutase, phosphomannomutase, and pho...
Saved in:
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BioMed Central
2014-12-01
|
| Series: | Genomics & Informatics |
| Subjects: | |
| Online Access: | http://genominfo.org/upload/pdf/gni-12-268.pdf |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832570510811070464 |
|---|---|
| author | Anayet Hasan Habibul Hasan Mazumder Arif Khan Mohammad Uzzal Hossain Homaun Kabir Chowdhury |
| author_facet | Anayet Hasan Habibul Hasan Mazumder Arif Khan Mohammad Uzzal Hossain Homaun Kabir Chowdhury |
| author_sort | Anayet Hasan |
| collection | DOAJ |
| description | The harshness of legionellosis differs from mild Pontiac fever to potentially fatal Legionnaire's disease. The increasing development of drug resistance against legionellosis has led to explore new novel drug targets. It has been found that phosphoglucosamine mutase, phosphomannomutase, and phosphoglyceromutase enzymes can be used as the most probable therapeutic drug targets through extensive data mining. Phosphoglucosamine mutase is involved in amino sugar and nucleotide sugar metabolism. The purpose of this study was to predict the potential target of that specific drug. For this, the 3D structure of phosphoglucosamine mutase of Legionella pneumophila (strain Paris) was determined by means of homology modeling through Phyre2 and refined by ModRefiner. Then, the designed model was evaluated with a structure validation program, for instance, PROCHECK, ERRAT, Verify3D, and QMEAN, for further structural analysis. Secondary structural features were determined through self-optimized prediction method with alignment (SOPMA) and interacting networks by STRING. Consequently, we performed molecular docking studies. The analytical result of PROCHECK showed that 95.0% of the residues are in the most favored region, 4.50% are in the additional allowed region and 0.50% are in the generously allowed region of the Ramachandran plot. Verify3D graph value indicates a score of 0.71 and 89.791, 1.11 for ERRAT and QMEAN respectively. Arg419, Thr414, Ser412, and Thr9 were found to dock the substrate for the most favorable binding of S-mercaptocysteine. However, these findings from this current study will pave the way for further extensive investigation of this enzyme in wet lab experiments and in that way assist drug design against legionellosis. |
| format | Article |
| id | doaj-art-8baaa0f29fff42a880abe5ca4f06a7a0 |
| institution | Kabale University |
| issn | 1598-866X 2234-0742 |
| language | English |
| publishDate | 2014-12-01 |
| publisher | BioMed Central |
| record_format | Article |
| series | Genomics & Informatics |
| spelling | doaj-art-8baaa0f29fff42a880abe5ca4f06a7a02025-02-02T15:38:29ZengBioMed CentralGenomics & Informatics1598-866X2234-07422014-12-0112426827510.5808/GI.2014.12.4.268119Molecular Characterization of Legionellosis Drug Target Candidate Enzyme Phosphoglucosamine Mutase from (strain Paris): An ApproachAnayet Hasan0Habibul Hasan Mazumder1Arif Khan2Mohammad Uzzal Hossain3Homaun Kabir Chowdhury4Department of Genetic Engineering and Biotechnology, Faculty of Biological Sciences, University of Chittagong, Chittagong 4331, Bangladesh.Department of Genetic Engineering and Biotechnology, Faculty of Biological Sciences, University of Chittagong, Chittagong 4331, Bangladesh.Department of Biotechnology and Genetic Engineering, Mawlana Bhashani Science and Technology University, Santosh, Tangail 1902, Bangladesh.Department of Biotechnology and Genetic Engineering, Mawlana Bhashani Science and Technology University, Santosh, Tangail 1902, Bangladesh.Biotechnology and Genetic Engineering Discipline, Khulna University, Khulna 9208, Bangladesh.The harshness of legionellosis differs from mild Pontiac fever to potentially fatal Legionnaire's disease. The increasing development of drug resistance against legionellosis has led to explore new novel drug targets. It has been found that phosphoglucosamine mutase, phosphomannomutase, and phosphoglyceromutase enzymes can be used as the most probable therapeutic drug targets through extensive data mining. Phosphoglucosamine mutase is involved in amino sugar and nucleotide sugar metabolism. The purpose of this study was to predict the potential target of that specific drug. For this, the 3D structure of phosphoglucosamine mutase of Legionella pneumophila (strain Paris) was determined by means of homology modeling through Phyre2 and refined by ModRefiner. Then, the designed model was evaluated with a structure validation program, for instance, PROCHECK, ERRAT, Verify3D, and QMEAN, for further structural analysis. Secondary structural features were determined through self-optimized prediction method with alignment (SOPMA) and interacting networks by STRING. Consequently, we performed molecular docking studies. The analytical result of PROCHECK showed that 95.0% of the residues are in the most favored region, 4.50% are in the additional allowed region and 0.50% are in the generously allowed region of the Ramachandran plot. Verify3D graph value indicates a score of 0.71 and 89.791, 1.11 for ERRAT and QMEAN respectively. Arg419, Thr414, Ser412, and Thr9 were found to dock the substrate for the most favorable binding of S-mercaptocysteine. However, these findings from this current study will pave the way for further extensive investigation of this enzyme in wet lab experiments and in that way assist drug design against legionellosis.http://genominfo.org/upload/pdf/gni-12-268.pdfdocking analysisdrug delivery systemshomology modelinglegionellosis |
| spellingShingle | Anayet Hasan Habibul Hasan Mazumder Arif Khan Mohammad Uzzal Hossain Homaun Kabir Chowdhury Molecular Characterization of Legionellosis Drug Target Candidate Enzyme Phosphoglucosamine Mutase from (strain Paris): An Approach Genomics & Informatics docking analysis drug delivery systems homology modeling legionellosis |
| title | Molecular Characterization of Legionellosis Drug Target Candidate Enzyme Phosphoglucosamine Mutase from (strain Paris): An Approach |
| title_full | Molecular Characterization of Legionellosis Drug Target Candidate Enzyme Phosphoglucosamine Mutase from (strain Paris): An Approach |
| title_fullStr | Molecular Characterization of Legionellosis Drug Target Candidate Enzyme Phosphoglucosamine Mutase from (strain Paris): An Approach |
| title_full_unstemmed | Molecular Characterization of Legionellosis Drug Target Candidate Enzyme Phosphoglucosamine Mutase from (strain Paris): An Approach |
| title_short | Molecular Characterization of Legionellosis Drug Target Candidate Enzyme Phosphoglucosamine Mutase from (strain Paris): An Approach |
| title_sort | molecular characterization of legionellosis drug target candidate enzyme phosphoglucosamine mutase from strain paris an approach |
| topic | docking analysis drug delivery systems homology modeling legionellosis |
| url | http://genominfo.org/upload/pdf/gni-12-268.pdf |
| work_keys_str_mv | AT anayethasan molecularcharacterizationoflegionellosisdrugtargetcandidateenzymephosphoglucosaminemutasefromstrainparisanapproach AT habibulhasanmazumder molecularcharacterizationoflegionellosisdrugtargetcandidateenzymephosphoglucosaminemutasefromstrainparisanapproach AT arifkhan molecularcharacterizationoflegionellosisdrugtargetcandidateenzymephosphoglucosaminemutasefromstrainparisanapproach AT mohammaduzzalhossain molecularcharacterizationoflegionellosisdrugtargetcandidateenzymephosphoglucosaminemutasefromstrainparisanapproach AT homaunkabirchowdhury molecularcharacterizationoflegionellosisdrugtargetcandidateenzymephosphoglucosaminemutasefromstrainparisanapproach |