Inspection of the residues that participate in the dimer interfac

Inspection of the residues that participate in the dimer interface of AlrSP on a structure-based sequence alignment (Figure 2) makes it apparent that that many of these residues are highly conserved, and also participate in substrate guidance (such as middle and inner entryway residues Tyr282′, Tyr352, Arg307′, Ile350, Arg288′, Asp170) or catalysis (e.g. Lys40, Tyr263′). Pentagonal water molecules in the active site

A cluster of hydrogen-bonded water molecules forms an ordered pentagonal ring and some adjacent partial rings in the active site entryways of both monomers of AlrSP (Figure 7). The pentagonal ring 4SC-202 supplier waters are located adjacent to the substrate binding site and between residues Tyr263″” and Tyr282″”. They are APR-246 ic50 positioned at the interface of monomer A and B and appear to be involved in the dimer interface, making direct or indirect hydrogen bonds with interface residues (Asp170, Tyr263′, Tyr282′,

selleck inhibitor Tyr288′, Arg307′, Tyr352). The distance between the water oxygen atoms that form each side of the pentagon is about 2.7 Å. The pentagonal ring is hydrogen-bonded directly to the protein at five atoms (Tyr282′ OH, Arg307′ NH1, and Arg288′ NH2 and NE from the entryway inner and middle layers, and Val308′

O) and makes hydrogen bonds with other waters both deeper in the active site and at the outer region of the entryway. Figure 7 Pentagonal ring waters near the substrate Parvulin binding site in alanine racemase from S. pneumoniae. The electron density 2Fo-Fc map is contoured at 0.8σ. Residues are shown as sticks, red spheres represent water molecules, and dashed yellow lines represent hydrogen bonds. Residues from the first monomer are colored pink, residues from the second monomer are blue and are denoted with primed numbers. The PLP-bound Lys residue (LLP) is grey. For simplicity, only some of the residues are shown. The hydrogen bond network we have identified could be facilitating substrate movement or proton transfer into the active site. Analysis of conserved water sites in AlrGS has been reported previously and the authors postulated that these sites could be involved in proton transfer or solvent shift into the active site [57]. In the high resolution structure of the protein crambin, Teeter reported pentagonal rings of water molecules which were felt to have a role in stabilizing protein structure or in catalysis [58].

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