TITLE

Insight to structural subsite recognition in plant thiol protease-inhibitor complexes : Understanding the basis of differential inhibition and the role of water

AUTHOR(S)
Bhattacharya, Suparna; Ghosh, Sreya; Chakraborty, Sibani; Bera, Asim K.; Mukhopadhayay, Bishnu P.; Dey, Indrani; Banerjee, Asok
PUB. DATE
January 2001
SOURCE
BMC Structural Biology;2001, Vol. 1, p4
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
Background: This work represents an extensive MD simulation / water-dynamics studies on a series of complexes of inhibitors (leupeptin, E-64, E-64-C, ZPACK) and plant cysteine proteases (actinidin, caricain, chymopapain, calotropin DI) of papain family to understand the various interactions, water binding mode, factors influencing it and the structural basis of differential inhibition. Results: The tertiary structure of the enzyme-inhibitor complexes were built by visual interactive modeling and energy minimization followed by dynamic simulation of 120 ps in water environment. DASA study with and without the inhibitor revealed the potential subsite residues involved in inhibition. Though the interaction involving main chain atoms are similar, critical inspection of the complexes reveal significant differences in the side chain interactions in S2-P2 and S3-P3 pairs due to sequence differences in the equivalent positions of respective subsites leading to differential inhibition. Conclusion: The key finding of the study is a conserved site of a water molecule near oxyanion hole of the enzyme active site, which is found in all the modeled complexes and in most crystal structures of papain family either native or complexed. Conserved water molecules at the ligand binding sites of these homologous proteins suggest the structural importance of the water, which changes the conventional definition of chemical geometry of inhibitor binding domain, its shape and complimentarity. The water mediated recognition of inhibitor to enzyme subsites (Pn...H2O....Sn) of leupeptin acetyl oxygen to caricain, chymopapain and calotropinDI is an additional information and offer valuable insight to potent inhibitor design.
ACCESSION #
29323525

 

Related Articles

  • A RasMol study of the Mechanism of Inhibition of Cysteine Endopeptidase Enzyme Papain. Subramani, Karthikeyan // Current Proteomics;Oct2009, Vol. 6 Issue 3, p198 

    Cysteine endopeptidases regulate many physiological processes in the body and their impaired function may lead to several diseases. One of the methods of treating such diseases is achieved by controlling the proteolytic activity of these enzymes by using enzyme inhibition. This manuscript...

  • Occupational asthma after inhalation of dust of the proteolytic enzyme, papain Brand, S.; Milne, J. // British Journal of Industrial Medicine;Nov1975, Vol. 32 Issue 4, p302 

    No abstract available.

  • papain.  // Taber's Cyclopedic Medical Dictionary (2009);2009, Issue 21, p1697 

    A definition of the term "papain," which refers to a proteolytic enzyme, is presented.

  • Evidence for the absence of enzymatic reactions in the glassy state. A case study of xanthophyll cycle pigments in the desiccation-tolerant moss Syntrichia ruralis. Fernández-Marín, Beatriz; Kranner, Ilse; Sebastián, María San; Artetxe, Unai; Laza, José Manuel; Vilas, José Luis; Pritchard, Hugh W.; Nadajaran, Jayanthi; Míguez, Fátima; Becerril, José María; García-Plazaola, José Ignacio // Journal of Experimental Botany;Oct2013, Vol. 64 Issue 10, p3033 

    Desiccation-tolerant plants are able to withstand dehydration and resume normal metabolic functions upon rehydration. These plants can be dehydrated until their cytoplasm enters a ‘glassy state’ in which molecular mobility is severely reduced. In desiccation-tolerant seeds,...

  • Location and volume of the active site of chymotrypsin. Kostetsky, P. // Biochemistry (00062979);Apr2007, Vol. 72 Issue 4, p392 

    The active site of chymotrypsin molecule (approximated by a sphere with radius of 20 �) was taken as the largest cavity on the enzyme surface. The volume inside the approximating sphere is sufficient for placement of 95% of non-hydrogen atoms of the enzyme. The active site cavity is...

  • Enzyme solid-state support assays: a surface plasmon resonance and mass spectrometry coupled study of immobilized insulin degrading enzyme. Grasso, Giuseppe; Bush, Ashley I.; D'Agata, Roberta; Rizzarelli, Enrico; Spoto, Giuseppe // European Biophysics Journal;Apr2009, Vol. 38 Issue 4, p407 

    Solid-support based assays offer several advantages that are not normally available in solution. Enzymes that are anchored on gold surfaces can interact with several different molecules, opening the way to high throughput array format based assays. In this scenario, surface plasmon resonance...

  • Efficient global geometry optimization of clusters: Method, and application to water clusters. Hartke, B. // European Physical Journal D -- Atoms, Molecules, Clusters & Opti;Jun2003, Vol. 24 Issue 1-3, p57 

    The method of global geometry optimization of atomic and molecular clusters by evolutionary algorithms is briefly presented and reviewed. As an exemplary application of a parallelized implementation of such an algorithm, neutral pure water clusters are globally optimized. In contrast to previous...

  • Atoms and molecules. Ward, Brian // First Fun Science Encyclopedia;2003, p13 

    This article focuses on atoms and molecules. The electrons are arranged like the planets that fly around the sun. It seems odd to compare a precious diamond with a lump of common coal, but they are, in fact, very similar. In coal, the atoms of carbon are joined up in one particular way. One...

  • The open-shell coupled-cluster method: Excitation energies and ionization potentials of H2O. Kaldor, Uzi // Journal of Chemical Physics;7/1/1987, Vol. 87 Issue 1, p467 

    The open-shell coupled cluster method is used to calculate directly several electronic excitation energies and ionization potentials of the water molecule. Correlation effects are included by summing single and double virtual excitations to infinite order. Triple excitations are treated...

Share

Read the Article

Courtesy of VIRGINIA BEACH PUBLIC LIBRARY AND SYSTEM

Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics