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Structural and functional insights into Mimivirus ORFans.
BMC Genomics. 2007 May 09; 8:115.BG

Abstract

BACKGROUND

Mimivirus isolated from A. polyphaga is the largest virus discovered so far. It is unique among all the viruses in having genes related to translation, DNA repair and replication which bear close homology to eukaryotic genes. Nevertheless, only a small fraction of the proteins (33%) encoded in this genome has been assigned a function. Furthermore, a large fraction of the unassigned protein sequences bear no sequence similarity to proteins from other genomes. These sequences are referred to as ORFans. Because of their lack of sequence similarity to other proteins, they can not be assigned putative functions using standard sequence comparison methods. As part of our genome-wide computational efforts aimed at characterizing Mimivirus ORFans, we have applied fold-recognition methods to predict the structure of these ORFans and further functions were derived based on conservation of functionally important residues in sequence-template alignments.

RESULTS

Using fold recognition, we have identified highly confident computational 3D structural assignments for 21 Mimivirus ORFans. In addition, highly confident functional predictions for 6 of these ORFans were derived by analyzing the conservation of functional motifs between the predicted structures and proteins of known function. This analysis allowed us to classify these 6 previously unannotated ORFans into their specific protein families: carboxylesterase/thioesterase, metal-dependent deacetylase, P-loop kinases, 3-methyladenine DNA glycosylase, BTB domain and eukaryotic translation initiation factor eIF4E.

CONCLUSION

Using stringent fold recognition criteria we have assigned three-dimensional structures for 21 of the ORFans encoded in the Mimivirus genome. Further, based on the 3D models and an analysis of the conservation of functionally important residues and motifs, we were able to derive functional attributes for 6 of the ORFans. Our computational identification of important functional sites in these ORFans can be the basis for a subsequent experimental verification of our predictions. Further computational and experimental studies are required to elucidate the 3D structures and functions of the remaining Mimivirus ORFans.

Authors+Show Affiliations

Computer Science and Engineering Dept., University at Buffalo, Buffalo, NY 14260-2000, USA. hksaini@cse.buffalo.edu <hksaini@cse.buffalo.edu>No affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17490476

Citation

Saini, Harpreet Kaur, and Daniel Fischer. "Structural and Functional Insights Into Mimivirus ORFans." BMC Genomics, vol. 8, 2007, p. 115.
Saini HK, Fischer D. Structural and functional insights into Mimivirus ORFans. BMC Genomics. 2007;8:115.
Saini, H. K., & Fischer, D. (2007). Structural and functional insights into Mimivirus ORFans. BMC Genomics, 8, 115.
Saini HK, Fischer D. Structural and Functional Insights Into Mimivirus ORFans. BMC Genomics. 2007 May 9;8:115. PubMed PMID: 17490476.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Structural and functional insights into Mimivirus ORFans. AU - Saini,Harpreet Kaur, AU - Fischer,Daniel, Y1 - 2007/05/09/ PY - 2007/02/08/received PY - 2007/05/09/accepted PY - 2007/5/11/pubmed PY - 2007/6/7/medline PY - 2007/5/11/entrez SP - 115 EP - 115 JF - BMC genomics JO - BMC Genomics VL - 8 N2 - BACKGROUND: Mimivirus isolated from A. polyphaga is the largest virus discovered so far. It is unique among all the viruses in having genes related to translation, DNA repair and replication which bear close homology to eukaryotic genes. Nevertheless, only a small fraction of the proteins (33%) encoded in this genome has been assigned a function. Furthermore, a large fraction of the unassigned protein sequences bear no sequence similarity to proteins from other genomes. These sequences are referred to as ORFans. Because of their lack of sequence similarity to other proteins, they can not be assigned putative functions using standard sequence comparison methods. As part of our genome-wide computational efforts aimed at characterizing Mimivirus ORFans, we have applied fold-recognition methods to predict the structure of these ORFans and further functions were derived based on conservation of functionally important residues in sequence-template alignments. RESULTS: Using fold recognition, we have identified highly confident computational 3D structural assignments for 21 Mimivirus ORFans. In addition, highly confident functional predictions for 6 of these ORFans were derived by analyzing the conservation of functional motifs between the predicted structures and proteins of known function. This analysis allowed us to classify these 6 previously unannotated ORFans into their specific protein families: carboxylesterase/thioesterase, metal-dependent deacetylase, P-loop kinases, 3-methyladenine DNA glycosylase, BTB domain and eukaryotic translation initiation factor eIF4E. CONCLUSION: Using stringent fold recognition criteria we have assigned three-dimensional structures for 21 of the ORFans encoded in the Mimivirus genome. Further, based on the 3D models and an analysis of the conservation of functionally important residues and motifs, we were able to derive functional attributes for 6 of the ORFans. Our computational identification of important functional sites in these ORFans can be the basis for a subsequent experimental verification of our predictions. Further computational and experimental studies are required to elucidate the 3D structures and functions of the remaining Mimivirus ORFans. SN - 1471-2164 UR - https://www.unboundmedicine.com/medline/citation/17490476/Structural_and_functional_insights_into_Mimivirus_ORFans_ L2 - https://bmcgenomics.biomedcentral.com/articles/10.1186/1471-2164-8-115 DB - PRIME DP - Unbound Medicine ER -