Conformational fluctuation in palladium(II)-methyl aldopentopyranoside complexes.

Four methyl d-pentopyranosides (ß-Ara, α-Lyx, ß-Rib, ß-Xyl), as well as Me-ß-l-Ara, some of them residing in a well-defined conformation in the solution state (Ara, Xyl) and some showing pronounced chair inversion in solution (Lyx, Rib), form bidentate chelates of the general formula [Pd(chxn)(LH₋2)-κO,O'] and [Pd(tmen)(LH₋2)-κO,O'], chxn=(R,R)-cyclohexane-1,2-diamine, tmen=N,N,N',N'-ethane-1,2-diamine and L=glycoside, with Pd(II)N2-type metal probes. The dynamic behaviour of the free glycosides is maintained in their chelates, the only case where the metal is bonded by a cis-vicinal diol function. Thus, one fluctuating chelate was detected with the lyxopyranoside in the κO(2,3) binding mode, and two fluctuating chelates were found for the ribopyranoside (κO(2,3) and κO(3,4)). No fluctuating chelate was found for the arabinopyranoside (the free arabinopyranoside being non-fluctuating as well), or for the xylopyranoside (no cis-vicinal diol function). In addition, syn-diaxial chelation (κO(2,4)) was observed for the ribopyranoside and the xylopyranoside. The spectroscopic results were supplemented by X-ray analyses.

Bidentate palladium(II) chelation by the common aldoses.

The [Pd(II){(R,R)-chxn}(OH)(2)] reagent (chxn=1,2-diaminocyclohexane) is introduced as a metal probe for the detection of the bidentate chelating sites of a glycose. Two moles of hydroxide per mole palladium support double deprotonation of potentially chelating diol functions at a glycose's backbone. The individual chelating sites are detected using one- and two-dimensional NMR techniques. At equimolar amounts of palladium(II) and aldose, the metal-binding sites include mostly the hydroxy function at the anomeric carbon atom. Chelators are derived from both the pyranose and the furanose isomers. Most pyranose-based chelators form five-membered chelate rings by using their 1,2-diol function. Though 1,2-diolate bonding is also common to the furanoses, the formation of six-membered chelate rings by 1,3-bonding is more significant for them. Metal-excess conditions provoke mostly bis-bidentate 1,2;3,4-chelation but unusual isomers form also: thus d-xylose is dimetallated in its all-axial beta-pyranose form, and erythrose's dimetallation results in the formation of two isomers of a metal derivative of the open-chain hydrate. The spectroscopic results are supported by crystal-structure determinations on [Pd{(R,R)-chxn}(alpha-D-Xylp1,2H(-2)-kappaO(1,2))].H(2)O (Xyl=xylose), [Pd{(R,R)-chxn}(alpha-D-Ribp1,2H(-2)-kappaO(1,2))].2.25H(2)O (Rib=ribose), [Pd{(R,R)-chxn}(alpha-L-Thrf1,3H(-2)-kappaO(1,3))].2H(2)O (Thr=threose) and [Pd{(R,R)-chxn}(alpha-D-Eryf1,3H(-2)-kappaO(1,3))].3H(2)O (Ery=erythrose).

Catalytic domain of MMP20 (Enamelysin) - the NMR structure of a new matrix metalloproteinase.

The solution structure of the catalytic domain of MMP-20, a member of the matrix metalloproteinases family not yet structurally characterized, complexed with N-Isobutyl-N-(4-methoxyphenylsulfonyl)glycyl hydroxamic acid (NNGH), is here reported and compared with other MMPs-NNGH adducts. The backbone dynamic has been characterized as well. We have found that, despite the same fold and very high overall similarity, the present structure experiences specific structural and dynamical similarities with some MMPs and differences with others, around the catalytic cavity. The present solution structure, not only contributes to fill the gap of structural knowledge on human MMPs, but also provides further information to design more selective and efficient inhibitors for a specific member of this class of proteins.

Fragment docking to S100 proteins reveals a wide diversity of weak interaction sites.

The S100 protein family is a highly conserved group of Ca(2+)-binding proteins that belong to the EF-hand type and are considered potential drug targets. In the present study we focused our attention on two members of the family: S100A13 and S100B; the former is involved in the nonclassical protein release of two proangiogenic polypeptides FGF-1 and IL-1alpha that are involved in inflammatory processes, whereas S100B is known to interact with the C-terminal domain of the intracellular tumor suppressor p53 and promote cancer development. We screened, using waterLOGSY NMR experiments, 430 molecules of a generic fragment library and we identified different hits for each protein. The subset of fragments interacting with S100B has very few members in common with the subset interacting with S100A13. From the (15)N-HSQC NMR spectra of the proteins in the presence of those hits the chemical shift differences Deltadelta(HN) were calculated, and the main regions of surface interaction were identified. A relatively large variety of interaction regions for various ligands were identified for the two proteins, including known or suggested protein-protein interaction sites.