Double-stranded DNA bacteriophage prohead protease is homologous to herpesvirus protease

Hua Cheng, Nan Shen, Jimin Pei, Nick V. Grishin

Research output: Contribution to journalArticlepeer-review

56 Scopus citations


Double-stranded DNA bacteriophages and herpesviruses assemble their heads in a similar fashion; a preformed precursor called a prohead or procapsid undergoes a conformational transition to give rise to a mature head or capsid. A virus-encoded prohead or procapsid protease is often required in this maturation process. Through computational analysis, we infer homology between bacteriophage prohead proteases (MEROPS families U9 and U35) and herpesvirus protease (MEROPS family S21), and unify them into a procapsid protease superfamily. We also extend this superfamily to include an uncharacterized cluster of orthologs (COG3566) and many other phage or bacteria-encoded hypothetical proteins. On the basis of this homology and the herpesvirus protease structure and catalytic mechanism, we predict that bacteriophage prohead proteases adopt the herpesvirus protease fold and exploit a conserved Ser and His residue pair in catalysis. Our study provides further support for the proposed evolutionary link between dsDNA bacteriophages and herpesviruses.

Original languageEnglish (US)
Pages (from-to)2260-2269
Number of pages10
JournalProtein Science
Issue number8
StatePublished - Aug 2004


  • Evolution
  • Gene organization
  • Homology detection
  • Prohead protease
  • Structure prediction
  • dsDNA bacteriophage

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology


Dive into the research topics of 'Double-stranded DNA bacteriophage prohead protease is homologous to herpesvirus protease'. Together they form a unique fingerprint.

Cite this