Binding Site Similarity Search to Identify Novel Target–Ligand Complexes

2013 ◽  
pp. 183-206
Keyword(s):  
Binding Site ◽  
Similarity Search ◽  
Binding Site Similarity ◽  
Novel Target

scholarly journals BSSF: a fingerprint based ultrafast binding site similarity search and function analysis server

2010 ◽  
Vol 11 (1) ◽  
Author(s):  
Bing Xiong ◽  
Jie Wu ◽  
David L Burk ◽  
Mengzhu Xue ◽  
Hualiang Jiang ◽  
...  
Keyword(s):  
Binding Site ◽  
Similarity Search ◽  
Function Analysis ◽  
Binding Site Similarity ◽  
And Function

Supersites within superfolds. Binding site similarity in the absence of homology 1 1Edited by J. Thornton

1998 ◽  
Vol 282 (4) ◽  
pp. 903-918 ◽  
Author(s):  
Robert B. Russell ◽  
Peter D. Sasieni ◽  
Michael J.E. Sternberg
Keyword(s):  
Binding Site ◽  
Binding Site Similarity

Role of the Oxyanion Binding Site and Subsites S1 and S2 in the Catalysis of Oligopeptidase B, a Novel Target for Antimicrobial Chemotherapy†

Biochemistry ◽  
2002 ◽  
Vol 41 (12) ◽  
pp. 4096-4106 ◽  
Author(s):  
Tünde Juhász ◽  
Zoltán Szeltner ◽  
Veronika Renner ◽  
László Polgár
Keyword(s):  
Binding Site ◽  
Antimicrobial Chemotherapy ◽  
Oligopeptidase B ◽  
Novel Target

scholarly journals The Poisson Index: a new probabilistic model for protein–ligand binding site similarity

2007 ◽  
Vol 23 (22) ◽  
pp. 3001-3008 ◽  
Author(s):  
J.R. Davies ◽  
R.M. Jackson ◽  
K.V. Mardia ◽  
C.C. Taylor
Keyword(s):  
Ligand Binding ◽  
Binding Site ◽  
Probabilistic Model ◽  
Ligand Binding Site ◽  
Binding Site Similarity

scholarly journals A VP2/3-derived peptide exhibits potent antiviral activity against BK and JC polyomaviruses by targeting a novel VP1 binding site

2019 ◽  
Author(s):  
Joshua R. Kane ◽  
Susan Fong ◽  
Jacob Shaul ◽  
Alexandra Frommlet ◽  
Andreas O. Frank ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
Binding Site ◽  
Viral Entry ◽  
Specific Binding ◽  
Peptide Binding ◽  
Structural Protein ◽  
Amino Acid Peptide ◽  
Peptide Binding Site ◽  
Concomitant Reduction ◽  
Novel Target

ABSTRACTIn pursuit of effective therapeutics for human polyomaviruses, we identified a peptide derived from the BK polyomavirus (BKV) minor structural proteins VP2/3 that is a potent inhibitor of BKV infection with no observable cellular toxicity. The thirteen amino acid peptide binds to major structural protein VP1 in a new location within the pore with a low nanomolar KD. Alanine scanning of the peptide identified three key residues, substitution of each of which results in ∼1000-fold loss of affinity with a concomitant reduction in antiviral activity. NMR spectroscopy and an X-ray structurally-guided model demonstrate specific binding of the peptide to the pore of the VP1 pentamer that constitutes the BKV capsid. Cell-based assays with the peptide demonstrate nanomolar inhibition of BKV infection and suggest that the peptide likely blocks the viral entry pathway between endocytosis and escape from the host cell ER. The peptide motif is highly conserved among the polyomavirus clade, and homologous peptides exhibit similar binding properties for JC polyomavirus and inhibit infection with similar potency to BKV in a model cell line. Substitutions within VP1 or VP2/3 residues involved in VP1-peptide interaction negatively impact viral infectivity, potentially indicating the peptide-binding site within the VP1 pore is relevant for VP1-VP2/3 interactions. The inhibitory potential of the peptide-binding site first reported here may present a novel target for development of new anti-polyomavirus therapies. In summary, we present the first anti-polyomavirus inhibitor that acts via a novel mechanism of action by specifically targeting the pore of VP1.

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