A “structural” water molecule in the family of fatty acid binding proteins

Likić, Vladimir A; Juranić, Nenad; Macura, Slobodan; Prendergast, Franklyn G.

doi:10.1110/ps.9.3.497

Cited by 49 publications

(34 citation statements)

References 37 publications

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“…These observations are in contrast with data obtained on rI-FABP both from crystal (Likic et al, 2000) and MD data analyses (Bakowies and van Gunsteren, 2002a). The authors identified, respectively, approx.…”

Section: Resultscontrasting

confidence: 89%

Structural and dynamic roles of permanent water molecules in ligand molecular recognition by chicken liver bile acid binding protein

Ricchiuto¹,

Rocco²,

Gianazza³

et al. 2008

J of Molecular Recognition

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Chicken liver bile acid binding protein (cL-BABP) crystallizes with water molecules in its binding site. To obtain insights on the role of internal water, we performed two 100 ns molecular dynamics (MD) simulations in explicit solvent for cL-BABP, as apo form and as a complex with two molecules of cholic acid, and analyzed in detail the dynamics properties of all water molecules. The diffusion coefficients of the more persistent internal water molecules are significantly different from the bulk, but similar between the two protein forms. A different number of molecules and a different organization are observed for apo- and holo-cL-BABP. Most water molecules identified in the binding site of the apo-crystal diffuse to the bulk during the simulation. In contrast, almost all the internal waters of the holo-crystal maintain the same interactions with internal sidechains and ligands, which suggests they have a relevant role in protein-ligand molecular recognition. Only in the presence of these water molecules we were able to reproduce, by a classical molecular docking approach, the structure of the complex cL-BABP::cholic acid with a low ligand root mean square deviation (RMSD) with respect to its reference positioning. Literature data reported a conserved pattern of hydrogen bonds between a single water molecule and three amino acid residues of the binding site in a series of crystallized FABP. In cL-BABP, the interactions between this conserved water molecule and the three residues are present in the crystal of both apo- and holo-cL-BABP but are lost immediately after the start of molecular dynamics.

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Section: Resultscontrasting

confidence: 89%

Structural and dynamic roles of permanent water molecules in ligand molecular recognition by chicken liver bile acid binding protein

Ricchiuto¹,

Rocco²,

Gianazza³

et al. 2008

J of Molecular Recognition

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“…A conserved structural water molecule in the FABP family has also been reported; P2 was not analyzed in that study [57]. This water is located in a pocket close to the protein external surface, in a wedge formed by the loop between β-strands D and E. From the human P2 structure, it is evident that this water molecule is also present, being H-bonded to the backbone NH group of Val84 and the carbonyl oxygens of Lys65 and Gln68 (data not shown).…”

Section: Resultsmentioning

confidence: 93%

Structural and Functional Characterization of Human Peripheral Nervous System Myelin Protein P2

et al. 2010

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The myelin sheath is a tightly packed multilayered membrane structure insulating selected axons in the central and the peripheral nervous systems. Myelin is a biochemically unique membrane, containing a specific set of proteins. In this study, we expressed and purified recombinant human myelin P2 protein and determined its crystal structure to a resolution of 1.85 Å. A fatty acid molecule, modeled as palmitate based on the electron density, was bound inside the barrel-shaped protein. Solution studies using synchrotron radiation indicate that the crystal structure is similar to the structure of the protein in solution. Docking experiments using the high-resolution crystal structure identified cholesterol, one of the most abundant lipids in myelin, as a possible ligand for P2, a hypothesis that was proven by fluorescence spectroscopy. In addition, electrostatic potential surface calculations supported a structural role for P2 inside the myelin membrane. The potential membrane-binding properties of P2 and a peptide derived from its N terminus were studied. Our results provide an enhanced view into the structure and function of the P2 protein from human myelin, which is able to bind both monomeric lipids inside its cavity and membrane surfaces.

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“…Prendergast's group21, 36 has extensively studied a conserved, internal solvent site in fatty‐acid binding proteins using NMR, molecular dynamics simulations, and analysis of crystal structure data. In our study, this site corresponded to the top peak in the water distribution map (62σ), and the site had 100% conservation [Table II, Fig.…”

Section: Resultsmentioning

confidence: 99%

“…One hypothesis is that structurally and functionally important water molecules occupy solvent sites that are highly conserved among proteins sharing a common three‐dimensional fold or active site structure. Conserved solvent sites have been examined only in a few protein families, such as fatty‐acid binding proteins,21 cytochrome c ,22 lectins,23 phospholipase A 2 ,24 ribonucleases,25 Rossmann dinucleotide‐binding proteins,3 serine proteases,13, 26, 27 and parvalbumins 28…”

Section: Introductionmentioning

confidence: 99%

Exploring structurally conserved solvent sites in protein families

2006

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Protein-bound water molecules are important components of protein structure, and therefore, protein function and energetics. Although structural conservation of solvent has been studied in a few protein families, a lack of suitable computational tools has hindered more comprehensive analyses. Herein we present a semiautomated computational approach for identifying solvent sites that are conserved among proteins sharing a common three-dimensional structure. This method is tested on six protein families: (1) monodomain cytochrome c, (2) fatty-acid binding protein, (3) lactate/malate dehydrogenase, (4) parvalbumin, (5) phospholipase A2, and (6) serine protease. For each family, the method successfully identified previously known conserved solvent sites. Moreover, the method discovered 22 novel conserved solvent sites, some of which have higher degrees of conservation than the previously known sites. All six families studied had solvent sites with more than 90% conservation and these sites were invariably located in regions of the protein with very high sequence conservation. These results suggest that highly conserved solvent sites, by virtue of their proximity to conserved residues, should be considered as one of the defining three-dimensional structural characteristics of protein families and folds.

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A “structural” water molecule in the family of fatty acid binding proteins

Cited by 49 publications

References 37 publications

Structural and dynamic roles of permanent water molecules in ligand molecular recognition by chicken liver bile acid binding protein

Structural and dynamic roles of permanent water molecules in ligand molecular recognition by chicken liver bile acid binding protein

Structural and Functional Characterization of Human Peripheral Nervous System Myelin Protein P2

Exploring structurally conserved solvent sites in protein families

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