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

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

Research output: Contribution to journalArticlepeer-review

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/.

Original languageEnglish
Article number16806
JournalScientific Reports
Volume12
Issue number1
DOIs
StatePublished - Dec 2022

Bibliographical note

Funding Information:
We thank Drs. Jonathan Kurie from MD Anderson Cancer Center, Emilia Galperin, Trevor Creamer, Louis B. Hersh, Craig Vander Kooi and Matthew Gentry from the University of Kentucky for sharing equipment, reagents, and helpful discussions. We thank Dr. Trevor Romsdahl for assistance with the LCMS analysis. This work was supported by the National Institutes of Health Grant R00CA225633 (H.G.). H.G. was also supported by the University of Kentucky Center for Cancer and Metabolism, funded through the NIH/NIGMS COBRE program under grant number P20 GM121327. WKR and the UTMB Mass Spectrometry Facility receives support from Cancer Prevention Research Institute of Texas (CPRIT) grant number RP190682. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. We thank the University of Kentucky Center for Computational Sciences and Information Technology Services Research Computing for their support and use of the Lipscomb Compute Cluster and associated research computing resources.

Funding Information:
We thank Drs. Jonathan Kurie from MD Anderson Cancer Center, Emilia Galperin, Trevor Creamer, Louis B. Hersh, Craig Vander Kooi and Matthew Gentry from the University of Kentucky for sharing equipment, reagents, and helpful discussions. We thank Dr. Trevor Romsdahl for assistance with the LCMS analysis. This work was supported by the National Institutes of Health Grant R00CA225633 (H.G.). H.G. was also supported by the University of Kentucky Center for Cancer and Metabolism, funded through the NIH/NIGMS COBRE program under grant number P20 GM121327. WKR and the UTMB Mass Spectrometry Facility receives support from Cancer Prevention Research Institute of Texas (CPRIT) grant number RP190682. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. We thank the University of Kentucky Center for Computational Sciences and Information Technology Services Research Computing for their support and use of the Lipscomb Compute Cluster and associated research computing resources.

Publisher Copyright:
© 2022, The Author(s).

ASJC Scopus subject areas

  • General

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