The protease and the assembly protein of Kaposi's sarcoma-associated herpesvirus (human herpesvirus 8)

Ünal, Ayçe; Pray, Todd; Lagunoff, Michael; Pennington, Michael W.; Ganem, Don; Craik, Charles S.

doi:10.1128/jvi.71.9.7030-7038.1997

Cited by 44 publications

(21 citation statements)

References 68 publications

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“…orf21, the thymidine kinase, and orf9, the DNA polymerase), glycoproteins (e.g. gB/orf8, gH/orf22, gM/orf38) and a viral proteinase and assembly protein (orf17) 108,118,119 . Genes not present in other herpesviruses, the ‘non‐conserved’ genes, are organized into five blocks (A–E) and can be further distinguished in viral genes (virus homologue of cellular genes, v‐ genes ) also found in other rhadinoviruses (e.g.…”

Section: Pathogenesismentioning

confidence: 99%

Kaposi's sarcoma: aetiopathogenesis, histology and clinical features

Buonaguro¹,

Tornesello²,

Buonaguro³

et al. 2003

Acad Dermatol Venereol

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This article should enable the reader: (i) to learn about the clinical and molecular aspects of KS in order to have a multidisciplinary approach to a tumour that shows unique features; (ii) to consider the role of viral agents and immunity; and (iii) to recognize properties of an opportunistic neoplasm. The identification of the HHV-8 role in KS pathogenesis should establish a relevant tool in the clinical management of KS patients.

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Section: Pathogenesismentioning

confidence: 99%

Kaposi's sarcoma: aetiopathogenesis, histology and clinical features

Buonaguro¹,

Tornesello²,

Buonaguro³

et al. 2003

Acad Dermatol Venereol

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“…E. coli Donaghy & Jupp ( 1995) HHV-6 E. coli Tigue et al (1996) HHV-8 E. coli Unal et al (1997) Figure 1. The basic steps in herpesvirus replication (a) Viral entry and protein synthesis.…”

Section: Ebvmentioning

confidence: 99%

The Herpesvirus Proteases as Targets for Antiviral Chemotherapy

Waxman

Darke

2000

Antivir Chem Chemother

118

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Viruses of the family Herpesviridae are responsible for a diverse set of human diseases. The available treatments are largely ineffective, with the exception of a few drugs for treatment of herpes simplex virus (HSV) infections. For several members of this DNA virus family, advances have been made recently in the biochemistry and structural biology of the essential viral protease, revealing common features that may be possible to exploit in the development of a new class of anti-herpesvirus agents. The herpesvirus proteases have been identified as belonging to a unique class of serine protease, with a Ser-His-His catalytic triad. A new, single domain protein fold has been determined by X-ray crystallography for the proteases of at least three different herpesviruses. Also unique for serine proteases, dimerization has been shown to be required for activity of the cytomegalovirus and HSV proteases. The dimerization requirement seriously impacts methods needed for productive, functional analysis and inhibitor discovery. The conserved functional and catalytic properties of the herpesvirus proteases lead to common considerations for this group of proteases in the early phases of inhibitor discovery. In general, classical serine protease inhibitors that react with active site residues do not readily inactivate the herpesvirus proteases. There has been progress however, with activated carbonyls that exploit the selective nucleophilicity of the active site serine. In addition, screening of chemical libraries has yielded novel structures as starting points for drug development. Recent crystal structures of the herpesvirus proteases now allow more direct interpretation of ligand structure-activity relationships. This review first describes basic functional aspects of herpesvirus protease biology and enzymology. Then we discuss inhibitors identified to date and the prospects for their future development.

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“…2). In this context, it might also be of value to compare the kinetic parameters for substrate hydrolysis by an Asp102His mutant of chymotrypsin or trypsin [16]with those of a wild‐type herpesvirus proteinase, such as that from HHV‐6. The orientation of the catalytic Ser,His,His residues in the herpesvirus proteinases may require additional features to contribute to the stabilisation that is achieved so readily by the classical serine proteinases.…”

Section: Discussionmentioning

confidence: 99%

Active site mutants of human herpesvirus‐6 proteinase

Tigue

Kay

1998

FEBS Letters

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Amino acid residues thought to comprise the catalytic triad of HHV-6 proteinase were changed by site-directed mutagenesis in the precursor form of the proteinase. By monitoring the ability of each mutant proteinase precursor to undergo autoprocessing, Ser116, His46 and His135 were identified as catalytically crucial. An attempt was made to mimic the catalytic triad arrangement of archetypal serine proteinases by replacement of the second histidine, His135, by an Asp. Instead of increasing the autoprocessing ability of the His135Asp mutant HHV-6 proteinase precursor, this mutation had a detrimental effect since the precursor persisted predominantly in its unprocessed form.z 1998 Federation of European Biochemical Societies.

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The protease and the assembly protein of Kaposi's sarcoma-associated herpesvirus (human herpesvirus 8)

Cited by 44 publications

References 68 publications

Kaposi's sarcoma: aetiopathogenesis, histology and clinical features

Kaposi's sarcoma: aetiopathogenesis, histology and clinical features

The Herpesvirus Proteases as Targets for Antiviral Chemotherapy

Active site mutants of human herpesvirus‐6 proteinase

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