Thiosemicarbazones (TSCs) possess significant antimalarial properties believed to be linked to the inhibition of major cysteine proteases, such as falcipain-2, in Plasmodium falciparum. However, the binding modes of TSCs to the active site of these enzymes are not clear. As a result of this, the nature of the bonding interactions between the active site of falcipain-2 and different derivatives ...

Hydrogenase enzymes are important because they can reversibly catalyze the production of molecular hydrogen. Proton transport mechanisms have been previously studied in residue pathways that lead to the active site of the enzyme via residues Cys299 and Ser319. The importance of this pathway and these residues has been previously exhibited through site-specific mutations, which were shown to int...

The oxidative degradation of biphenyl and polychlorinated biphenyls (PCBs) is initiated in Pandoraea pnomenusa B-356 by biphenyl dioxygenase (BPDO(B356)). BPDO(B356), a heterohexameric (αβ)(3) Rieske oxygenase (RO), catalyzes the insertion of dioxygen with stereo- and regioselectivity at the 2,3-carbons of biphenyl, and can transform a broad spectrum of PCB congeners. Here we present the X-ray ...

Crystal structures of hen egg-white lysozyme (HEWL) determined under pressures ranging from ambient pressure to 950 MPa are presented. From 0.1 to 710 MPa, the molecular and internal cavity volumes are monotonically compressed. However, from 710 to 890 MPa the internal cavity volume remains almost constant. Moreover, as the pressure increases to 950 MPa, the tetragonal crystal of HEWL undergoes...

One of the most conserved glycosylation sites of neuraminidase (NA) is 146-N-glycan. This site is adjacent to the 150-cavity of NA, which is found within the active site and thought to be a target for rational drug development against the antiviral resistance of influenza. Here, through a total of 2.4 μs molecular dynamics (MD) simulations, we demonstrated that 146-N-glycan can stabilize the co...

Mutant forms of thymidylate synthase (TS) with substitutions at the conserved active site residue, Trp 80, are deficient in the hydride transfer step of the TS reaction. These mutants produce a beta-mercaptoethanol (beta-ME) adduct of the 2'-deoxyuridine-5'-monophosphate (dUMP) exocyclic methylene intermediate. Trp 80 has been proposed to assist hydride transfer by stabilizing a 5,6,7,8-tetrahy...

The homodimeric enzyme form of quinoprotein ethanol dehydrogenase from Pseudomonas aeruginosa ATCC 17933 crystallizes readily with the space group R3. The X-ray structure was solved at 2.6 A resolution by molecular replacement. Aside from differences in some loops, the folding of the enzyme is very similar to the large subunit of the quinoprotein methanol dehydrogenases from Methylobacterium ex...

The complementary spatial relationship between fullerene C(60) and the hydrophobic cavity region of the human immunodeficiency virus (HIV) protease, which houses the active site of the enzyme, has led to the suggestion that fullerene-based derivatives could have potential use as effective HIV protease inhibitors. The ability of such compounds to desolvate the cavity region leads to a strong hyd...

The outer membrane of gram-negative bacteria forms a permeability barrier that usually reduces the access of antibiotics to intracellular targets and renders gram-negative bacteria less susceptible to antibiotics than gram-positive bacteria, which lack an outer membrane. However, gram-negative bacteria become highly susceptible to antibiotics if the antibiotics are actively transported across t...