Glucokinase is a monomeric enzyme that displays a low affinity for glucose and a sigmoidal saturation curve for its substrate, two properties that are important for its playing the role of a glucose sensor in pancreas and liver. The molecular basis for these two properties is not well understood. Herein we report the crystal structures of glucokinase in its active and inactive forms, which demonstrate that global conformational change, including domain reorganization, is induced by glucose binding. This suggests that the positive cooperativity of monomeric glucokinase obeys the "mnemonical mechanism" rather than the well-known concerted model. These structures also revealed an allosteric site through which small molecules may modulate the kinetic properties of the enzyme. This finding provided the mechanistic basis for activation of glucokinase as a potential therapeutic approach for treating type 2 diabetes mellitus.

Spectral sensitization of a mesoporous graphite carbon nitride (mpg-C(3)N(4)) photocatalyst was investigated by depositing magnesium phthalocyanine (MgPc) to expand the absorption to wavelengths longer than those of the principal mpg-C(3)N(4). The obtained sample, MgPc/Pt/mpg-C(3)N(4) (Pt as a cocatalyst) showed stable photocatalytic evolution of hydrogen from aqueous solution in the presence of sacrificial reagents (triethanolamine), even under irradiation at wavelengths longer than 600 nm. Increasing the amount of MgPc led to ordered MgPc aggregation on the photocatalyst surfaces. The rate of photocatalytic hydrogen evolution was highest on a sample with an amount of MgPc corresponding to a monolayer on the Pt/mpg-C(3)N(4) photocatalyst surface. The obtained action spectra of hydrogen evolution and the observation that the amount of evolved hydrogen substantially surpassed the amount of MgPc, confirm that the introduced MgPc functioned as a photocatalytic sensitizer.

To determine the superconducting gap function of YNi2B2C, the c-axis thermal conductivity kappa(zz) was measured in H rotated in various directions. The angular variation of kappa(zz) in H rotated within the ab plane shows a peculiar fourfold oscillation with narrow cusps. The amplitude of this fourfold oscillation becomes very small when H is rotated conically around the c axis with a tilt angle of 45 degrees. These results provide the first compelling evidence that the gap function has point nodes located along the a and b axes. This unprecedented gap structure challenges the current view on the pairing mechanism.

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Factor Xa, the converting enzyme of prothrombin to thrombin, has emerged as an alternative (to thrombin) target for drug discovery for thromboembolic diseases. An inhibitor has been synthesized and the crystal structure of the complex between Des[1-44] factor Xa and the inhibitor has been determined by crystallographic methods in two different crystal forms to 2.3-and 2.4-Å resolution. The racemic mixture of inhibitor FX-2212, (2RS)-(3-amidino-3-biphenylyl)-5-(4-pyridylamino)pentanoic acid, inhibits factor Xa activity by 50% at 272 nM in vitro. The S-isomer of FX-2212 (FX-2212a) was found to bind to the active site of factor Xa in both crystal forms. The biphenylamidine of FX-2212a occupies the S1-pocket, and the pyridine ring makes hydrophobic interactions with the factor Xa aryl-binding site. Several water molecules meditate inhibitor binding to residues in the active site. In contrast to the earlier crystal structures of factor Xa, such as those of apo-Des[1-45] factor Xa and Des[1-44] factor Xa in complex with a naphthyl inhibitor DX-9065a, two epidermal growth factor-like domains of factor Xa are well ordered in both our crystal forms as well as the region between the two domains, which recently was found to be the binding site of the effector cell protease receptor-1. This structure provides a basis for designing next generation inhibitors of factor Xa.Thromboembolic disease is caused by the improper functioning of the blood coagulation process. Blood clots are formed by a zymogen activation cascade of serine proteases, and the last protease of the cascade, thrombin, converts fibrinogen to fibrin, which cross-links to form blood clots (for a review, see ref.