A relatively short catch-up, with much more to come�
Martina Havenith at Bochum and her colleagues have extended their previous work on the mechanism of antifreeze proteins. Previously they looked at an antifreeze glycoprotein and found, using terahertz spectroscopy, that ice-binding by the protein seems to involve a long-range retardation of water H-bond dynamics, extending up to 2 nm from the molecular surface (S. Ebbinghaus et al., JACS 132, 12210; 2010). Now they find a similar effect operating for the antifreeze protein (AFP) of the fire-coloured beetle D. canadensis, a hyperactive insect (K. Meister et al., PNAS 110, 1617; 2013 � paper here). This contrasts, however, with the mechanism of another class of AFP, called wfAFP-1, which seems to operate only by short-ranged water binding to surface OH groups (S. Ebbinghaus et al., Biophys. J. 103, L20; 2012). As the authors say, �Nature is probably more inventive than initially thought and makes use of short- and long-range water perturbation to varying degrees in different classes of AFPs�.
Meanwhile, Ido Braslavsky of Ohio University and colleagues have used microfluidic methods to study the effects of AFPs on ice nucleation, and find that the growth of ice crystals is inhibited by the irreversible surface binding of the proteins (Y. Celik et al., PNAS 110, 1309; 2013 � paper here). These results help to rule out suggestions that direct binding of the AFPs to ice is not necessary to their mode of action.
More cases of water assisting receptor-substrate recognition and catalytic activity. First, Stephen Neidle at UCL and colleagues find that a cluster of 11 water molecules in an AT region of the minor groove of DNA seems to support the binding of three different small-molecule ligands (D.-G. Wei et al., JACS 135, 1369; 2013 � paper here). This cluster stabilizes the ligand by hydrogen bonding, and is also linked to (but distinct from) the well-known spine of hydration in B-DNA. Slight differences in binding mode with this cluster seem to account for the differences in binding affinity of the ligands: in other words, it is the water network that is calling the shots.
Second, Xiaoqing Wang and Hajime Hirao at Nanyang Technological University in Singapore say that the catalysis of myo-inositol monophosphatase (IMPase, a potential target for lithium treatment of bipolar disorder) is dependent on two bound water molecules (J. Phys. Chem. B 117, 833; 2012 � paper here). One provides the hydroxide ion that attacks the bound substrate. The other, coordinated to a magnesium ion, facilitates proton transfer leading to the product.
There seems to be an increasing perception that understanding the collective vibrations of proteins � their softness or rigidity � could offer insights into their enzymatic activity. Sow-Hsin Chen at MIT and coworkers support that view with an X-ray scattering study of the collective modes of hydrated lysozyme (Z. Wang et al., J. Phys. Chem. B 117, 1186; 2013 � paper here). They find that at low hydration levels both the collective �soft� phonon modes and the enzymatic activity are much weaker or absent, suggesting a causal relationship: an indicator of the now familiar plasticizing effect of hydration.
C. Cametti at �La Sapienza� University of Rome and colleagues consider another aspect of protein hydration: how high concentrations of the protein (again lysozyme) can lead to clustering and a consequent decrease in average hydration number (C. Cametti et al., J. Phys. Chem. B 117, 104; 2013 � paper here). Their measurements of the dielectric spectra from 500 MHz to 50 GHz, which probe orientational relaxation, are consistent with this hypothesis of clustering into small aggregates at concentrations above about 100 mg/mL, which was first proposed by Stradner et al. (Nature 432, 492; 2004).
There is now some debate about whether the proposed two metastable liquid phases and associated critical point claimed on the basis of some simulations is real or not. That has been disputed by David Limmer and David Chandler at Berkeley, who extend their previous negative results using several different water potentials in a new preprint. I have written a commentary on the issue here.
Martina Havenith at Bochum and her colleagues have extended their previous work on the mechanism of antifreeze proteins. Previously they looked at an antifreeze glycoprotein and found, using terahertz spectroscopy, that ice-binding by the protein seems to involve a long-range retardation of water H-bond dynamics, extending up to 2 nm from the molecular surface (S. Ebbinghaus et al., JACS 132, 12210; 2010). Now they find a similar effect operating for the antifreeze protein (AFP) of the fire-coloured beetle D. canadensis, a hyperactive insect (K. Meister et al., PNAS 110, 1617; 2013 � paper here). This contrasts, however, with the mechanism of another class of AFP, called wfAFP-1, which seems to operate only by short-ranged water binding to surface OH groups (S. Ebbinghaus et al., Biophys. J. 103, L20; 2012). As the authors say, �Nature is probably more inventive than initially thought and makes use of short- and long-range water perturbation to varying degrees in different classes of AFPs�.
Meanwhile, Ido Braslavsky of Ohio University and colleagues have used microfluidic methods to study the effects of AFPs on ice nucleation, and find that the growth of ice crystals is inhibited by the irreversible surface binding of the proteins (Y. Celik et al., PNAS 110, 1309; 2013 � paper here). These results help to rule out suggestions that direct binding of the AFPs to ice is not necessary to their mode of action.
More cases of water assisting receptor-substrate recognition and catalytic activity. First, Stephen Neidle at UCL and colleagues find that a cluster of 11 water molecules in an AT region of the minor groove of DNA seems to support the binding of three different small-molecule ligands (D.-G. Wei et al., JACS 135, 1369; 2013 � paper here). This cluster stabilizes the ligand by hydrogen bonding, and is also linked to (but distinct from) the well-known spine of hydration in B-DNA. Slight differences in binding mode with this cluster seem to account for the differences in binding affinity of the ligands: in other words, it is the water network that is calling the shots.
Second, Xiaoqing Wang and Hajime Hirao at Nanyang Technological University in Singapore say that the catalysis of myo-inositol monophosphatase (IMPase, a potential target for lithium treatment of bipolar disorder) is dependent on two bound water molecules (J. Phys. Chem. B 117, 833; 2012 � paper here). One provides the hydroxide ion that attacks the bound substrate. The other, coordinated to a magnesium ion, facilitates proton transfer leading to the product.
There seems to be an increasing perception that understanding the collective vibrations of proteins � their softness or rigidity � could offer insights into their enzymatic activity. Sow-Hsin Chen at MIT and coworkers support that view with an X-ray scattering study of the collective modes of hydrated lysozyme (Z. Wang et al., J. Phys. Chem. B 117, 1186; 2013 � paper here). They find that at low hydration levels both the collective �soft� phonon modes and the enzymatic activity are much weaker or absent, suggesting a causal relationship: an indicator of the now familiar plasticizing effect of hydration.
C. Cametti at �La Sapienza� University of Rome and colleagues consider another aspect of protein hydration: how high concentrations of the protein (again lysozyme) can lead to clustering and a consequent decrease in average hydration number (C. Cametti et al., J. Phys. Chem. B 117, 104; 2013 � paper here). Their measurements of the dielectric spectra from 500 MHz to 50 GHz, which probe orientational relaxation, are consistent with this hypothesis of clustering into small aggregates at concentrations above about 100 mg/mL, which was first proposed by Stradner et al. (Nature 432, 492; 2004).
There is now some debate about whether the proposed two metastable liquid phases and associated critical point claimed on the basis of some simulations is real or not. That has been disputed by David Limmer and David Chandler at Berkeley, who extend their previous negative results using several different water potentials in a new preprint. I have written a commentary on the issue here.
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