Comparative genomic and biochemical analyses identify a collagen galactosylhydroxylysyl glucosyltransferase from Acanthamoeba polyphaga mimivirus

Abstract Humans and Acanthamoeba polyphaga mimivirus share numerous homologous genes, including collagens and collagen-modifying enzymes. To explore this homology, we performed a genome-wide comparison between human and mimivirus using DELTA-BLAST (Domain Enhanced Lookup Time Accelerated BLAST) and...

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Main Authors: Wenhui Wu, Jeong Seon Kim, Aaron O. Bailey, William K. Russell, Stephen J. Richards, Tiantian Chen, Tingfei Chen, Zhenhang Chen, Bo Liang, Mitsuo Yamauchi, Houfu Guo
Format: Article
Language:English
Published: Nature Portfolio 2022-10-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-022-21197-1
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author Wenhui Wu
Jeong Seon Kim
Aaron O. Bailey
William K. Russell
Stephen J. Richards
Tiantian Chen
Tingfei Chen
Zhenhang Chen
Bo Liang
Mitsuo Yamauchi
Houfu Guo
author_facet Wenhui Wu
Jeong Seon Kim
Aaron O. Bailey
William K. Russell
Stephen J. Richards
Tiantian Chen
Tingfei Chen
Zhenhang Chen
Bo Liang
Mitsuo Yamauchi
Houfu Guo
author_sort Wenhui Wu
collection DOAJ
description Abstract Humans and Acanthamoeba polyphaga mimivirus share numerous homologous genes, including collagens and collagen-modifying enzymes. To explore this homology, we performed a genome-wide comparison between human and mimivirus using DELTA-BLAST (Domain Enhanced Lookup Time Accelerated BLAST) and identified 52 new putative mimiviral proteins that are homologous with human proteins. To gain functional insights into mimiviral proteins, their human protein homologs were organized into Gene Ontology (GO) and REACTOME pathways to build a functional network. Collagen and collagen-modifying enzymes form the largest subnetwork with most nodes. Further analysis of this subnetwork identified a putative collagen glycosyltransferase R699. Protein expression test suggested that R699 is highly expressed in Escherichia coli, unlike the human collagen-modifying enzymes. Enzymatic activity assay and mass spectrometric analyses showed that R699 catalyzes the glucosylation of galactosylhydroxylysine to glucosylgalactosylhydroxylysine on collagen using uridine diphosphate glucose (UDP-glucose) but no other UDP-sugars as a sugar donor, suggesting R699 is a mimiviral collagen galactosylhydroxylysyl glucosyltransferase (GGT). To facilitate further analysis of human and mimiviral homologous proteins, we presented an interactive and searchable genome-wide comparison website for quickly browsing human and Acanthamoeba polyphaga mimivirus homologs, which is available at RRID Resource ID: SCR_022140 or https://guolab.shinyapps.io/app-mimivirus-publication/ .
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spelling doaj.art-cb6af35921514888996b0d19a1c51b8e2022-12-22T02:24:09ZengNature PortfolioScientific Reports2045-23222022-10-0112111210.1038/s41598-022-21197-1Comparative genomic and biochemical analyses identify a collagen galactosylhydroxylysyl glucosyltransferase from Acanthamoeba polyphaga mimivirusWenhui Wu0Jeong Seon Kim1Aaron O. Bailey2William K. Russell3Stephen J. Richards4Tiantian Chen5Tingfei Chen6Zhenhang Chen7Bo Liang8Mitsuo Yamauchi9Houfu Guo10Department of Molecular and Cellular Biochemistry, University of KentuckyDepartment of Molecular and Cellular Biochemistry, University of KentuckyDepartment of Biochemistry and Molecular Biology, University of Texas Medical BranchDepartment of Biochemistry and Molecular Biology, University of Texas Medical BranchDepartment of Molecular and Cellular Biochemistry, University of KentuckyDepartment of Molecular and Cellular Biochemistry, University of KentuckyDepartment of Molecular and Cellular Biochemistry, University of KentuckyDepartment of Biochemistry, Emory University School of MedicineDepartment of Biochemistry, Emory University School of MedicineDivision of Oral and Craniofacial Health Sciences, Adams School of Dentistry, University of North Carolina at Chapel HillDepartment of Molecular and Cellular Biochemistry, University of KentuckyAbstract Humans and Acanthamoeba polyphaga mimivirus share numerous homologous genes, including collagens and collagen-modifying enzymes. To explore this homology, we performed a genome-wide comparison between human and mimivirus using DELTA-BLAST (Domain Enhanced Lookup Time Accelerated BLAST) and identified 52 new putative mimiviral proteins that are homologous with human proteins. To gain functional insights into mimiviral proteins, their human protein homologs were organized into Gene Ontology (GO) and REACTOME pathways to build a functional network. Collagen and collagen-modifying enzymes form the largest subnetwork with most nodes. Further analysis of this subnetwork identified a putative collagen glycosyltransferase R699. Protein expression test suggested that R699 is highly expressed in Escherichia coli, unlike the human collagen-modifying enzymes. Enzymatic activity assay and mass spectrometric analyses showed that R699 catalyzes the glucosylation of galactosylhydroxylysine to glucosylgalactosylhydroxylysine on collagen using uridine diphosphate glucose (UDP-glucose) but no other UDP-sugars as a sugar donor, suggesting R699 is a mimiviral collagen galactosylhydroxylysyl glucosyltransferase (GGT). To facilitate further analysis of human and mimiviral homologous proteins, we presented an interactive and searchable genome-wide comparison website for quickly browsing human and Acanthamoeba polyphaga mimivirus homologs, which is available at RRID Resource ID: SCR_022140 or https://guolab.shinyapps.io/app-mimivirus-publication/ .https://doi.org/10.1038/s41598-022-21197-1
spellingShingle Wenhui Wu
Jeong Seon Kim
Aaron O. Bailey
William K. Russell
Stephen J. Richards
Tiantian Chen
Tingfei Chen
Zhenhang Chen
Bo Liang
Mitsuo Yamauchi
Houfu Guo
Comparative genomic and biochemical analyses identify a collagen galactosylhydroxylysyl glucosyltransferase from Acanthamoeba polyphaga mimivirus
Scientific Reports
title Comparative genomic and biochemical analyses identify a collagen galactosylhydroxylysyl glucosyltransferase from Acanthamoeba polyphaga mimivirus
title_full Comparative genomic and biochemical analyses identify a collagen galactosylhydroxylysyl glucosyltransferase from Acanthamoeba polyphaga mimivirus
title_fullStr Comparative genomic and biochemical analyses identify a collagen galactosylhydroxylysyl glucosyltransferase from Acanthamoeba polyphaga mimivirus
title_full_unstemmed Comparative genomic and biochemical analyses identify a collagen galactosylhydroxylysyl glucosyltransferase from Acanthamoeba polyphaga mimivirus
title_short Comparative genomic and biochemical analyses identify a collagen galactosylhydroxylysyl glucosyltransferase from Acanthamoeba polyphaga mimivirus
title_sort comparative genomic and biochemical analyses identify a collagen galactosylhydroxylysyl glucosyltransferase from acanthamoeba polyphaga mimivirus
url https://doi.org/10.1038/s41598-022-21197-1
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