Record Details

Evidence for inhibitory interaction of hyaluronan binding protein 1 with S. pneumoniae hyaluronidase

NIPGR Digital Knowledge Repository (NDKR)

View Archive Info
 
 
Field Value
 
Title Evidence for inhibitory interaction of hyaluronan binding protein 1 with S. pneumoniae hyaluronidase
 
Creator Yadav, Gitanjali
Prasad, Ramachandra L. A.
Jha, Babal Kant
Rai, Vivek
Bhakuni, Vinod
Datta, Kasturi
 
Subject Streptococcus pneumoniae
Hyaluronidase
Hyaluronan-binding Protein
Inhibitory Interaction
 
Description Bacterial hyaluronan lyase enzymes are the major virulence
factors that enable greater microbial ingress by cleaving hyaluronan (HA) polymers present predominantly in extracellular
space of vertebrates. Based on the premise that effective inhibitors may bind to and stabilize HA thereby protecting it from
degradation, here we investigated inhibitory activity of human
hyaluronan-binding protein 1 (HABP1) on bacterial hyaluronidase because it is highly specific to HA and localized on the cell
surface. Biochemical characterization revealed that HABP1 is a
competitive inhibitor of Streptococcus pneumoniae hyaluronate
lyase (SpnHL) with an IC50 value of 22 uM. This is thus the first
report of an endogenous protein inhibitor that may be used dur-
ing natural antibacterial defense. Our findings also support a
novel multipronged mechanism for the high efficacy of HABP1-
mediated inhibition based on structural modeling of enzyme,
substrate, and inhibitor. Evidence from docking simulations
and contact interface interactions showed that the inherent
charge asymmetry of HABP1 plays a key role in the inhibitory
activity. This novel role of HABP1 may pave the way for peptide
inhibitors as alternatives to synthetic chemicals in antibacterial
research.
 
Date 2014-02-13T10:36:55Z
2014-02-13T10:36:55Z
2009
22 October 2008
 
Type Article
 
Identifier J. Biol. Chem., 284: 3897-3905
http://hdl.handle.net/123456789/134
 
Language en
 
Publisher The American Society for Biochemistry and Molecular Biology, Inc.