scholarly journals Conserved Water Molecules Stabilize the Ω-Loop in Class A β-Lactamases

2008 ◽  
Vol 52 (3) ◽  
pp. 1072-1079 ◽  
Author(s):  
Fabian Bös ◽  
Jürgen Pleiss
Keyword(s):  
Phylogenetic Analysis ◽  
High Resolution ◽  
Evolutionary Relationship ◽  
Water Molecules ◽  
Protein Residues ◽  
Class A ◽  
Conserved Water Molecules ◽  
Dense Cluster ◽  
The Relationship

ABSTRACT A set of 49 high-resolution (≤2.2 Å) structures of the TEM, SHV, and CTX-M class A β-lactamase families was systematically analyzed to investigate the role of conserved water molecules in the stabilization of the Ω-loop. Overall, 13 water molecules were found to be conserved in at least 45 structures, including two water positions which were found to be conserved in all structures. Of the 13 conserved water molecules, 6 are located at the Ω-loop, forming a dense cluster with hydrogen bonds to residues at the Ω-loop as well as to the rest of the protein. This layer of conserved water molecules is packed between the Ω-loop and the rest of the protein and acts as structural glue, which could reduce the flexibility of the Ω-loop. A correlation between conserved water molecules and conserved protein residues could in general not be detected, with the exception of the conserved water molecules at the Ω-loop. Furthermore, the evolutionary relationship between the three families, derived from the number of conserved water molecules, is similar to the relationship derived from phylogenetic analysis.

scholarly journals The role of conserved water molecules in the catalytic domain of protein kinases

2009 ◽  
Vol 76 (3) ◽  
pp. 527-535 ◽  
Author(s):  
James D. R. Knight ◽  
Donald Hamelberg ◽  
J. Andrew McCammon ◽  
Rashmi Kothary
Keyword(s):  
Protein Kinases ◽  
Catalytic Domain ◽  
Water Molecules ◽  
Conserved Water Molecules

scholarly journals Electrochemistry of well-defined graphene samples: role of contaminants

2014 ◽  
Vol 172 ◽  
pp. 261-272 ◽  
Author(s):  
Hollie V. Patten ◽  
Matěj Velický ◽  
Nick Clark ◽  
Christopher A. Muryn ◽  
Ian A. Kinloch ◽  
...  
Keyword(s):  
High Resolution ◽  
Methyl Methacrylate ◽  
High Purity ◽  
Graphene Layer ◽  
Electrochemical Activity ◽  
Small Scale ◽  
Mechanical Exfoliation ◽  
The Relationship ◽  
Electrochemical Characterisation

We report the electrochemical characterisation of well-defined graphene samples, prepared by mechanical exfoliation. Mechanical exfoliation is the method of choice for high purity graphene samples, despite the inherent complexity of the approach and the small scale of the resultant flakes. However, one important, yet presently unclear area, is the role of adsorbates such as processing residue, on the properties of the graphene layer. We report high resolution microscopic and electrochemical characterisation of a variety of poly(methyl methacrylate) (PMMA) transferred graphene samples, with the explicit aim of investigating the relationship between electrochemical activity and sample purity.

scholarly journals Tunable allosteric library of caspase-3 identifies coupling between conserved water molecules and conformational selection

2016 ◽  
Vol 113 (41) ◽  
pp. E6080-E6088 ◽  
Author(s):  
Joseph J. Maciag ◽  
Sarah H. Mackenzie ◽  
Matthew B. Tucker ◽  
Joshua L. Schipper ◽  
Paul Swartz ◽  
...  
Keyword(s):  
High Resolution ◽  
Posttranslational Modifications ◽  
Caspase 3 ◽  
High Energy ◽  
Water Molecules ◽  
Active Conformation ◽  
Allosteric Site ◽  
Dimer Interface ◽  
Conformational Selection ◽  
Conserved Water Molecules

The native ensemble of caspases is described globally by a complex energy landscape where the binding of substrate selects for the active conformation, whereas targeting an allosteric site in the dimer interface selects an inactive conformation that contains disordered active-site loops. Mutations and posttranslational modifications stabilize high-energy inactive conformations, with mostly formed, but distorted, active sites. To examine the interconversion of active and inactive states in the ensemble, we used detection of related solvent positions to analyze 4,995 waters in 15 high-resolution (<2.0 Å) structures of wild-type caspase-3, resulting in 450 clusters with the most highly conserved set containing 145 water molecules. The data show that regions of the protein that contact the conserved waters also correspond to sites of posttranslational modifications, suggesting that the conserved waters are an integral part of allosteric mechanisms. To test this hypothesis, we created a library of 19 caspase-3 variants through saturation mutagenesis in a single position of the allosteric site of the dimer interface, and we show that the enzyme activity varies by more than four orders of magnitude. Altogether, our database consists of 37 high-resolution structures of caspase-3 variants, and we demonstrate that the decrease in activity correlates with a loss of conserved water molecules. The data show that the activity of caspase-3 can be fine-tuned through globally desolvating the active conformation within the native ensemble, providing a mechanism for cells to repartition the ensemble and thus fine-tune activity through conformational selection.

CONSERVED WATER MOLECULES IN X-RAY STRUCTURES HIGHLIGHT THE ROLE OF WATER IN INTRAMOLECULAR AND INTERMOLECULAR INTERACTIONS

2008 ◽  
Vol 06 (04) ◽  
pp. 775-788 ◽  
Author(s):  
EVGENIY AKSIANOV ◽  
OLGA ZANEGINA ◽  
ALEXANDER GRISHIN ◽  
SERGEY SPIRIN ◽  
ANNA KARYAGINA ◽  
...  
Keyword(s):  
Intermolecular Interactions ◽  
Protein Interactions ◽  
Active Sites ◽  
Three Dimensional ◽  
Water Molecules ◽  
Macromolecular Complexes ◽  
X Ray ◽  
Conserved Water Molecules ◽  
Related Proteins

Water molecules immobilized on a protein or DNA surface are known to play an important role in intramolecular and intermolecular interactions. Comparative analysis of related three-dimensional (3D) structures allows to predict the locations of such water molecules on the protein surface. We have developed and implemented the algorithm WLAKE detecting "conserved" water molecules, i.e. those located in almost the same positions in a set of superimposed structures of related proteins or macromolecular complexes. The problem is reduced to finding maximal cliques in a certain graph. Despite exponential algorithm complexity, the program works appropriately fast for dozens of superimposed structures. WLAKE was used to predict functionally significant water molecules in enzyme active sites (transketolases) as well as in intermolecular (ETS–DNA complexes) and intramolecular (thiol–disulfide interchange protein) interactions. The program is available online at .

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