3N4P

Human cytomegalovirus terminase nuclease domain

Summary for 3N4P

• Entry DOI: 10.2210/pdb3n4p/pdb
• Related: 3N4Q
• Descriptor: Terminase subunit UL89 protein, MAGNESIUM ION (3 entities in total)
• Functional Keywords: terminase, nuclease, human cytomegalovirus, hcmv, herpesvirus, dna packaging, dna binding protein
• Biological source: Human herpesvirus 5
• Cellular location: Host nucleus (By similarity): P16732
• Total number of polymer chains: 4
• Total formula weight: 127441.69

Authors

Nadal, M.,Mas, P.J.,Blanco, A.G.,Arnan, C.,Sola, M.,Hart, D.J.,Coll, M. (deposition date: 2010-05-22, release date: 2010-10-06, Last modification date: 2024-02-21)

Primary citation

Nadal, M.,Mas, P.J.,Blanco, A.G.,Arnan, C.,Sola, M.,Hart, D.J.,Coll, M.
Structure and inhibition of herpesvirus DNA packaging terminase nuclease domain.
Proc.Natl.Acad.Sci.USA, 107:16078-16083, 2010

PubMed Abstract: During viral replication, herpesviruses package their DNA into the procapsid by means of the terminase protein complex. In human cytomegalovirus (herpesvirus 5), the terminase is composed of subunits UL89 and UL56. UL89 cleaves the long DNA concatemers into unit-length genomes of appropriate length for encapsidation. We used ESPRIT, a high-throughput screening method, to identify a soluble purifiable fragment of UL89 from a library of 18,432 randomly truncated ul89 DNA constructs. The purified protein was crystallized and its three-dimensional structure was solved. This protein corresponds to the key nuclease domain of the terminase and shows an RNase H/integrase-like fold. We demonstrate that UL89-C has the capacity to process the DNA and that this function is dependent on Mn(2+) ions, two of which are located at the active site pocket. We also show that the nuclease function can be inactivated by raltegravir, a recently approved anti-AIDS drug that targets the HIV integrase.

PubMed: 20805464
DOI: 10.1073/pnas.1007144107

Experimental method

X-RAY DIFFRACTION (2.15 Å)