This crystal structure will contribute useful information towards

This crystal selleck chemicals llc structure will contribute useful information towards our structure-based drug design research aimed at the identification and development of alanine racemase inhibitors. Results and discussion Structure determination and refinement Crystals of AlrSP suitable for X-ray diffraction were grown as described previously Selleck GSK1120212 [21]. Crystals diffracted to a resolution of 2.0 Å and belong to the space group P3121 with the unit cell parameters a = b = 119.97 Å, c = 118.10 Å, α = β =

90° and γ = 120°. The structure of AlrSP was solved by molecular replacement using CNS [42] and AlrGS (PDB ID 1SFT) [29] without the PLP cofactor as a search model. Refinement was carried out initially with CNS, then completed with TLS refinement [43] in Refmac5 [44]. After structure solution and refinement, the final model of AlrSP, validated using PROCHECK [45] has 92.7% of residues in the most favored regions of the Ramachandran plot, 6.9% of residues in the additionally allowed regions and 0.3% of residues in the generously allowed regions. The structure has root-mean-square (r.m.s.) deviations from ideality for bond lengths of 0.015 Å and for angles of 1.45°. Further data collection and refinement statistics are presented in Table 1. Table 1 Data collection and structure refinement statistics Data collection    Unit cell parameters    a = 119.97 Å, b = 119.97 Å, c = 118.10 Å      α

= 90°, β = 90°, γ = 120°    Space group    P3121    λ (Å)    1.5418    Mosaicity    0.48    Observations    475265    Unique reflections    66748    R-merge a (%)    8.3 selleck chemical (68.2)    Completeness (%)    99.6 (95.4)        21.3 (1.7) Refinement statistics    Resolution (Å)    23.03 – 2.00 (2.05 – 2.00)    Reflections    63336 (4412)    Total

atoms    6161    R-factorb (%)    16.8 (32.2)    Rfree (%)    20.0 (35.5)    Average B-factors (Å2)   Wilson B-factor    33.2 All atoms    42.7 Main chain atoms    41.8 Side chain atoms and waters    43.6 Waters    44.5 Edoxaban    R.m.s. deviations   Bond lengths (Å)    0.015 Bond angles (deg)    1.45    No. of residues    734, 100%    No. of protein atoms    5615    No. of PLP atoms    30    No. of benzoic acid atoms No. of water molecules    9 507 Residues in the Ramachandran plot      Most favored regions    588, 92.7%    Additionally allowed regions    44, 6.9%    Generously allowed regions    2, 0.3%    Disallowed regions    0, 0% a R-merge = Σ|I obs-I avg|/Σ|I avg| b R-factor = Σ|F obs-F calc|/Σ|F obs| Values in parenthesis are for the highest resolution shell. Overall structure of AlrSP AlrSP forms a homodimer in which the two monomers form a head-to-tail association, typical of that seen in other alanine racemases. Each monomer has an eight-stranded α/β barrel domain (residues 1-238) and an extended β-strand domain (residues 239-367) (Figure 1A). The α/β barrel of one monomer is in contact with the β-strand domain of the other monomer (Figure 1B).

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