Crystal structure of vaccinia virus uracil-DNA glycosylase reveals dimeric assembly-4

<p><b>Copyright information:</b></p><p>Taken from "Crystal structure of vaccinia virus uracil-DNA glycosylase reveals dimeric assembly"</p><p>http://www.biomedcentral.com/1472-6807/7/45</p><p>BMC Structural Biology 2007;7():45-45.</p><p>Published online 2 Jul 2007</p><p>PMCID:PMC1936997.</p><p></p>n the temperature-sensitive mutant D30 and shows the effect of the mutation. () Residues in this pocket are displayed as stick models and are labeled. () The pocket is shown in the same view as in Fig. 5A, but an Arg residue (color code: pink) in one rotamer conformation was modeled in place of G179 to indicate that a substitution at this position will introduce steric hindrance. In addition, other rotamer conformations that point towards residues F195 and I198 will position this charged residue even farther into the hydrophobic pocket. In the shown conformation, distances of side chain atoms of the modeled R179 are only 1.5–2.5 Å from surrounding residues

Crystal structure of vaccinia virus uracil-DNA glycosylase reveals dimeric assembly-2

<p><b>Copyright information:</b></p><p>Taken from "Crystal structure of vaccinia virus uracil-DNA glycosylase reveals dimeric assembly"</p><p>http://www.biomedcentral.com/1472-6807/7/45</p><p>BMC Structural Biology 2007;7():45-45.</p><p>Published online 2 Jul 2007</p><p>PMCID:PMC1936997.</p><p></p>ures were superimposed with TOPP [22]. () Active site of vvUDG. The active site of vvUDG with the glycerol (GOL) molecule at the center is shown in this stereo figure. The difference electron density for glycerol (F-Fomit map contoured at 3σ) is displayed (blue mesh). A second glycerol molecule away from the active site can also be seen. Active site residues are shown as stick models. () Active site of UDG (3EUG). Shown is a close-up view of the active site in UDG in the same orientation as the vvUDG in Fig. 3A. The bound glycerol (GOL) in the active site is shown in the center. Active site residues are shown as stick models. () Active site of vvUDG with modeled uracil. The active site of vvUDG was superimposed on the UDG active site containing uracil. The uracil molecule (URA) is modeled into the active site of vvUDG in the same position and orientation as seen in Fig. 3D for the structure (). The carbonyl oxygen atoms of uracil in this model superimpose with two hydroxyl groups in glycerol in the vvUDG structure. () Active site in UDG (). Shown is a close-up view of the active site in UDG with a bound uracil (URA) molecule in the same orientation as in Figs. 3A and 3B

Crystal structure of vaccinia virus uracil-DNA glycosylase reveals dimeric assembly-1

<p><b>Copyright information:</b></p><p>Taken from "Crystal structure of vaccinia virus uracil-DNA glycosylase reveals dimeric assembly"</p><p>http://www.biomedcentral.com/1472-6807/7/45</p><p>BMC Structural Biology 2007;7():45-45.</p><p>Published online 2 Jul 2007</p><p>PMCID:PMC1936997.</p><p></p>ture elements are labeled according to Fig. 1A. Helices are labeled α1 through α10 and strands are marked β1 through β10. The active site residues are displayed as stick models. Positions of mutations are also shown as stick models (color code: purple). () Type I dimer of vvUDG. The figure shows the type I dimer of vvUDG as observed in the asymmetric unit of the trigonal crystal form. The subunits (A and B) in this dimer are related by NCS. Active site residues and mutation site residues are shown as stick models as seen in (). () Type II dimer of vvUDG. The figure shows the type II dimer of vvUDG. These dimers are observed in the asymmetric unit of the orthorhombic crystal form (subunits related by NCS) and also in the unit cell of the trigonal crystal form (subunits related by crystallographic symmetry). The active site residues are displayed as stick models. Positions of mutations are also shown as stick models (color code: purple)

Crystal structure of vaccinia virus uracil-DNA glycosylase reveals dimeric assembly-0

<p><b>Copyright information:</b></p><p>Taken from "Crystal structure of vaccinia virus uracil-DNA glycosylase reveals dimeric assembly"</p><p>http://www.biomedcentral.com/1472-6807/7/45</p><p>BMC Structural Biology 2007;7():45-45.</p><p>Published online 2 Jul 2007</p><p>PMCID:PMC1936997.</p><p></p>ed secondary structure elements for the vvUDG monomer. The β-strands are labeled B1 through B10 and α helices are labeled H1 through H10. A β-hairpin turn between the two N-terminal β-strands B1 and B2 is also shown. The portions of the missing loop regions are indicated by spaces. Several residues of the N-terminal His-tag are visible in the structure. () Topology diagram for vvUDG. There are a total of 4 β-sheets (β-sheet 1: strands 1 and 2; β-sheet 2: strands 3 and 7; β-sheet 3: strands 4, 6, 8 and 9; β-sheet 4: strands 5 and 10). () Wiring plot for human UDG (PDBId: ). The figure shows the protein sequence overlaid with assigned secondary structure elements for human UDG. () Topology diagram for human UDG (PDBId: ). The figure was prepared using the PDBSUM server [39, 40]

Crystal structure of vaccinia virus uracil-DNA glycosylase reveals dimeric assembly-5

<p><b>Copyright information:</b></p><p>Taken from "Crystal structure of vaccinia virus uracil-DNA glycosylase reveals dimeric assembly"</p><p>http://www.biomedcentral.com/1472-6807/7/45</p><p>BMC Structural Biology 2007;7():45-45.</p><p>Published online 2 Jul 2007</p><p>PMCID:PMC1936997.</p><p></p>n the temperature-sensitive mutant Dand shows the effect of the mutation. () Residues in this pocket are displayed as stick models and are labeled. () The pocket is shown in the same view as in Fig. 6A, but a Phe residue (color code: pink) in a preferred rotamer conformation was modeled in place of L110 to indicate that a substitution at this position will introduce steric hindrance. In this conformation, distances of side chain atoms of the modeled F110 are only 2.6–2.8 Å from side chain atoms of I89 and I92

Crystal structure of vaccinia virus uracil-DNA glycosylase reveals dimeric assembly-3

<p><b>Copyright information:</b></p><p>Taken from "Crystal structure of vaccinia virus uracil-DNA glycosylase reveals dimeric assembly"</p><p>http://www.biomedcentral.com/1472-6807/7/45</p><p>BMC Structural Biology 2007;7():45-45.</p><p>Published online 2 Jul 2007</p><p>PMCID:PMC1936997.</p><p></p>and UDG and provides a model for the lack of inhibition of vvUDG by Ugi. () Superimposition of 'Leu intercalation' loops. The two superimposed loops are shown in different colors (vvUDG cyan; UDG green). L191 in UDG (green) and the corresponding residue R185 in vvUDG (cyan) are shown as stick models. Other loop residues are also shown and some of the loop residues are labeled. It can be seen that only the two N-terminal loop residues, Pro (vvUDG P182; UDG P188) and His (vvUDG H181; UDG H187), are identical in sequence and in similar orientations. () Close-up view of UDG:Ugi complex. The structure of vvUDG was superimposed onto the UDG structure in the UDG:Ugi complex. For the UDG proteins only the loop regions are shown (UDG in green, vvUDG in cyan), while for Ugi the semi-transparent surface of the binding pocket is shown (colored by element). The eight hydrophobic residues of Ugi (M24, V29, V32, I33, V43, M56, L58 and V71) that form the hydrophobic cavity and provide major interactions with the 'Leu intercalation' loop in UDG [19] are shown as stick models. The corresponding residues in the 'Leu intercalation' loop, L191 in UDG (green) and R185 in vvUDG (cyan), are shown as stick models. In UDG:Ugi complex L191 points into the hydrophobic pocket

Identification of Protein-Protein Interaction Inhibitors Targeting Vaccinia Virus Processivity Factor for Development of Antiviral Agents ▿ †

Poxvirus uracil DNA glycosylase D4 in association with A20 and the catalytic subunit of DNA polymerase forms the processive polymerase complex. The binding of D4 and A20 is essential for processive polymerase activity. Using an AlphaScreen assay, we identified compounds that inhibit protein-protein interactions between D4 and A20. Effective interaction inhibitors exhibited both antiviral activity and binding to D4. These results suggest that novel antiviral agents that target the protein-protein interactions between D4 and A20 can be developed for the treatment of infections with poxviruses, including smallpox

Crystal Structures of Group B Streptococcus Glyceraldehyde-3-Phosphate Dehydrogenase: Apo-Form, Binary and Ternary Complexes

<div><p>Glyceraldehyde 3-phosphate dehydrogenase or GAPDH is an evolutionarily conserved glycolytic enzyme. It catalyzes the two step oxidative phosphorylation of D-glyceraldehyde 3-phosphate into 1,3-bisphosphoglycerate using inorganic phosphate and NAD⁺ as cofactor. GAPDH of Group B Streptococcus is a major virulence factor and a potential vaccine candidate. Moreover, since GAPDH activity is essential for bacterial growth it may serve as a possible drug target. Crystal structures of Group B Streptococcus GAPDH in the apo-form, two different binary complexes and the ternary complex are described here. The two binary complexes contained NAD⁺ bound to 2 (mixed-holo) or 4 (holo) subunits of the tetrameric protein. The structure of the mixed-holo complex reveals the effects of NAD⁺ binding on the conformation of the protein. In the ternary complex, the phosphate group of the substrate was bound to the new Pi site in all four subunits. Comparison with the structure of human GAPDH showed several differences near the adenosyl binding pocket in Group B Streptococcus GAPDH. The structures also reveal at least three surface-exposed areas that differ in amino acid sequence compared to the corresponding areas of human GAPDH.</p></div