1NJT

COMPLEX STRUCTURE OF HCMV PROTEASE AND A PEPTIDOMIMETIC INHIBITOR


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.50 Å
  • R-Value Free: 0.271 
  • R-Value Work: 0.228 
  • R-Value Observed: 0.228 

wwPDB Validation   3D Report Full Report


This is version 1.4 of the entry. See complete history


Literature

Structural and Biochemical Studies of Inhibitor Binding to Human Cytomegalovirus Protease

Khayat, R.Batra, R.Qian, C.Halmos, T.Bailey, M.Tong, L.

(2003) Biochemistry 42: 885-891

  • DOI: https://doi.org/10.1021/bi027045s
  • Primary Citation of Related Structures:  
    1NJT, 1NJU, 1NKK, 1NKM

  • PubMed Abstract: 

    Herpesvirus protease is required for the life cycle of the virus and is an attractive target for the design and development of new anti-herpes agents. The protease belongs to a new class of serine proteases, with a novel backbone fold and a unique Ser-His-His catalytic triad. Here we report the crystal structures of human cytomegalovirus protease in complex with two peptidomimetic inhibitors. The structures reveal a new hydrogen-bonding interaction between the main chain carbonyl of the P(5) residue and the main chain amide of amino acid 137 of the protease, which is important for the binding affinity of the inhibitor. Conformational flexibility was observed in the S(3) pocket of the enzyme, and this is supported by our characterization of several mutants in this pocket. One of the structures is at 2.5 A resolution, allowing us for the first time to locate ordered solvent molecules in the inhibitor complex. The presence of two solvent molecules in the active site may have implications for the design of new inhibitors against this enzyme. Favorable and stereospecific interactions have been established in the S(1)' pocket for one of these inhibitors.


  • Organizational Affiliation

    Department of Biological Sciences, Columbia University, New York, New York 10027, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Capsid protein P40
A, B, C, D
256Human betaherpesvirus 5Mutation(s): 1 
Gene Names: UL80 OR APNG
EC: 3.4.21.97
UniProt
Find proteins for P16753 (Human cytomegalovirus (strain AD169))
Explore P16753 
Go to UniProtKB:  P16753
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP16753
Sequence Annotations
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  • Reference Sequence

Find similar proteins by:  Sequence   |   3D Structure  

Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Peptidomimetic Inhibitor
E, F, G, H
6N/AMutation(s): 0 
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Modified Residues  2 Unique
IDChains TypeFormula2D DiagramParent
DMH
Query on DMH
E, F, G, H
L-PEPTIDE LINKINGC6 H12 N2 O3ASN
DMK
Query on DMK
E, F, G, H
L-PEPTIDE LINKINGC6 H11 N O4ASP
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.50 Å
  • R-Value Free: 0.271 
  • R-Value Work: 0.228 
  • R-Value Observed: 0.228 
  • Space Group: P 21 21 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 107.072α = 90
b = 213.306β = 90
c = 52.795γ = 90
Software Package:
Software NamePurpose
CNSrefinement
DENZOdata reduction
SCALEPACKdata scaling
COMOphasing

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2003-02-11
    Type: Initial release
  • Version 1.1: 2008-04-29
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Atomic model, Database references, Derived calculations, Non-polymer description, Structure summary, Version format compliance
  • Version 1.3: 2013-02-27
    Changes: Other
  • Version 1.4: 2021-10-27
    Changes: Database references, Derived calculations