Unique fold and active site in cytomegalovirus protease

Qiu, Xiayang; Culp, Jeffrey S.; DiLella, Anthony G.; Hellmig, Brian D.; Hoog, Susan S.; Janson, Cheryl A.; Smith, Ward W.; Abdel-Meguid, Sherin S.

doi:10.1038/383275a0

Cited by 154 publications

(128 citation statements)

References 22 publications

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“…Among these are the proteinase and assembly proteins, both of which play essential roles in capsid assembly and maturation (Preston et al, 1983 ;Gao et al, 1994). They have been characterized from herpes simplex virus type 1 (HSV-1), human cytomegalovirus (HCMV) and Epstein-Barr virus (EBV) (Gibson et al, 1994 ;Donaghy & Jupp, 1995) and the three-dimensional structure of the HCMV proteinase has recently been solved (Chen et al, 1996 ;Qiu et al, 1996 ;Shieh et al, 1996 ;Tong et al, 1996). Sequence homology suggests that VZV genes 33 and 33.5 encode the VZV proteinase and assembly protein respectively (Welch et al, 1991 ;Gibson et al, 1994).…”

Section: Varicella-zoster Virus (Vzv) Is a Member Of Thementioning

confidence: 99%

Characterization of the proteinase specified by varicella-zoster virus gene 33.

McMillan

Kay²,

Mills³

1997

Journal of General Virology

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Varicella-zoster virus (VZV) genes 33 and 33.5 are predicted to encode the VZV proteinase and its substrate (the assembly protein) respectively. These genes were expressed in insect cells using recombinant baculovirus and it was confirmed that gene 33 encodes a proteinase capable of autoproteolytic processing at two positions. When VZV gene 33.5 was co-expressed with the VZV proteinase, processing of the VZV33.5 gene product was observed. A polyclonal antiserum to the VZV assembly protein domain highlighted a set of proteins in VZV infected HEL cells identical to those identified in insect cells expressing VZV genes 33 and 33.5. To facilitate further characterization of the VZV proteinase the enzyme was purified by affinity chromatography from an E. coli expression system and in vitro activity was observed.

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Section: Varicella-zoster Virus (Vzv) Is a Member Of Thementioning

confidence: 99%

Characterization of the proteinase specified by varicella-zoster virus gene 33.

McMillan

Kay²,

Mills³

1997

Journal of General Virology

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“…The amino-acid sequences of herpesvirus proteases have no detectable homology to other serine proteases or hydrolases. The crystal structure of HCMV protease has recently been determined in our laboratory by the seleno-methionyl multiple-wavelength anomalous diffraction (MAD) technique (Tong et al, 1996), and in other laboratories by the heavy-atom isomorphous replacement technique (Qiu et al, 1996;Shieh et al, 1996;Chen et al, 1996). It showed that HCMV protease possesses a new polypeptide backbone fold; confirmed that Ser132 and His63 are in close proximity in space; and identified His157 as the possible third member of the catalytic triad.…”

Section: Introductionmentioning

confidence: 94%

Experiences from the Structure Determination of Human Cytomegalovirus Protease

Tong

Qian²,

Davidson³

et al. 1997

Acta Cryst D

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Several obstacles were encountered and overcome during the structure determination of human cytomegalovirus protease. Dehydration of crystals, by exposing them to higher concentrations of the precipitant, reduced the mosaicity of the crystals and may have also resolved their microscopic twinning. The initial phase information was obtained with the selenomethionyl multiple-wavelength anomalous diffraction technique. However, site-specific mutagenesis was required to introduce extra Met residues into the protease. The phase information had to be improved by non-crystallographic symmetry averaging, initially among three 'crystal forms'. A change in the composition of the artificial mother liquor led to a significant improvement, from 3.0 and 2.0A resolution, in the diffraction quality of the crystals. The experiences reported here may prove useful to structure determination of other proteins.

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“…The first crystal structures of an assemblin were published by three groups in 1996 [58,59,83]. All three structures are of dimeric HCMV-assemblin.…”

Section: Structurementioning

confidence: 99%

Assemblins as maturational proteases in herpesviruses

Zühlsdorf

Hinrichs

2017

Journal of General Virology

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During assembly of herpesvirus capsids, a protein scaffold self-assembles to ring-like structures forming the scaffold of the spherical procapsids. Proteolytic activity of the herpesvirus maturational protease causes structural changes that result in angularization of the capsids. In those mature icosahedral capsids, the packaging of viral DNA into the capsids can take place. The strictly regulated protease is called assemblin. It is inactive in its monomeric state and activated by dimerization. The structures of the dimeric forms of several assemblins from all herpesvirus subfamilies have been elucidated in the last two decades. They revealed a unique serine-protease fold with a catalytic triad consisting of a serine and two histidines. Inhibitors that disturb dimerization by binding to the dimerization area were found recently. Additionally, the structure of the monomeric form of assemblin from pseudorabies virus and some monomer-like structures of Kaposi's sarcoma-associated herpesvirus assemblin were solved. These findings are the proof-of-principle for the development of new anti-herpesvirus drugs. Therefore, the most important information on this fascinating and unique class of proteases is summarized here.

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Unique fold and active site in cytomegalovirus protease

Cited by 154 publications

References 22 publications

Characterization of the proteinase specified by varicella-zoster virus gene 33.

Characterization of the proteinase specified by varicella-zoster virus gene 33.

Experiences from the Structure Determination of Human Cytomegalovirus Protease

Assemblins as maturational proteases in herpesviruses

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