Hai-Yang Yu

Structural mechanism of ring-opening reaction of glucose by human serum albumin

Background: Glucose can glycate human serum albumin (HSA), but the mechanism is unknown. Results: Crystal structures of rHSA in the presence of glucose show that glucose is linearized and covalently linked to rHSA. Conclusion: The residues Lys-195 and Lys-199 of rHSA are involved in glucose ring opening. Significance: This work provides a structural mechanism of protein glycation. Glucose reacts with proteins nonenzymatically under physiological conditions. Such glycation is exacerbated in diabetic patients with high levels of blood sugar and induces various complications. Human albumin serum (HSA) is the most abundant protein in plasma and is glycated by glucose. The glycation sites on HSA remain controversial among different studies. Here, we report two protein crystal structures of HSA in complex with either glucose or fructose. These crystal structures reveal the presence of linear forms of sugar for both monosaccharides. The linear form of glucose forms a covalent bond to Lys-195 of HSA, but this is not the case for fructose. Based on these structures, we propose a mechanism for glucose ring opening involving both residues Lys-195 and Lys-199. These results provide mechanistic insights to understand the glucose ring-opening reaction and the glycation of proteins by monosaccharides.

Structural Basis for Therapeutic Intervention of uPA/uPAR System

Urokinase-type plasminogen activator (uPA) is one of the two physiological serine proteases responsible for the activation of plasminongen to plasmin. uPA activity is regulated by its inhibitors (PAI-1 and PAI-2) and its receptor (uPAR), and an expanding list of their interacting proteins. In addition to plasminogen activation, this system also plays important roles in the regulation of many cellular processes including cell proliferation, adhesion and migration. It is beyond reasonable doubt that this enzyme system plays a central role in tumor biology and represents a high potential target for therapeutic intervention of tumor growth and metastasis. During the past fifteen years, crystal structures of uPA and its inhibitors have facilitated the development of uPA inhibitors. Many crystal structures of proteins in the uPA/uPAR system have also been reported recently, especially a series of structures of uPAR and its complexes with vitronectin and uPA, facilitating the development and evaluation of uPAR inhibitors. Recent progress on uPA inhibitors will be summarized in this article. The unique structural features and the druggable potentials of these new structures will also be discussed.

Hydrothermal synthesis of benzothiazole–carboxylic cadmium(II) coordination networks: pH-controlled topologies and compositional distributions

Using the hydrothermal synthetic method, two cadmium complexes (1 and 2) with an identical chemical formula of [Cd(ABTC)2]n (ABTC = 2-aminobenzothiazole-6-carboxylic acid) but completely different topologies were prepared at two different pH values of reaction solution, 5.3 and 7.3, respectively. Reaction with a pH in between resulted in a mixture of 1 and 2, and the ratio of two products was proportional to pH value of the reaction condition.

Ethyl 2-(tert-butoxy­carbonyl­amino)-1,3-benzothia­zole-6-carboxyl­ate

In the crystal of the title compound, C15H18N2O4S, inversion dimers are formed by intermolecular N—H⋯N hydrogen bonds and weak C—H⋯O contacts. These dimers stack up along [100] through inversion-related π–π interactions between thiazole rings [centroid–centroid distance = 3.790 (2) Å] and the thiazole and benzene rings [centroid–centroid distance = 3.845 (2) Å] and C—H⋯π contacts.

tert-Butyl N-[6-(N,N-dipropyl­carbamo­yl)-1,3-benzothia­zol-2-yl]carbamate

The title compound C19H27N3O3S, crystallizes with two unique molecules in the asymmetric unit. The benzene ring of each benzothiazole unit carries a dipropylcarbamoyl substituent in the 6-position and a tert-butyl carbamate unit on each thiazole ring. In the crystal structure, intermolecular N—H⋯N and weak C—H⋯O hydrogen bonds form centrosymmetric dimers. Additional C—H⋯O contacts construct a three-dimensional network. A very weak C—H⋯π contact is also present.

catena-Poly[lead(II)-bis-(μ-2-amino-1,3-benzothia-zole-6-carboxyl-ato)].

The title complex, [Pb(C8H5N2O2S)2]n, consists of one PbII ion located on a crystallographic twofold axis and two symmetry-related 2-amino-1,3-benzothiazole-6-carboxylate (ABTC) ligands. The central PbII ion has a (4 + 2) coordination by four O atoms of the two ABTC ligands and two weaker Pb—S bonding interactions (Pb—S secondary bonds) from S atoms of other two neighbouring ABTC ligands. These bonds link the metal ions into zigzag chains along the c axis, which, in turn, aggregate through π–π interactions [centroid–centroid distance = 3.7436 Å] between ABTC rings and N—H⋯O and N—H⋯N hydrogen bonds.

Tb3+- and Yb3+-doped novel KBaLu(MoO4)3 crystals with disordered chained structure showing down- and up-conversion luminescence

In this study, a novel dual-mode luminescence phosphor KBaLu(MoO4)3:Tb3+,Yb3+ has been synthesized by high-temperature solid-state reactions, and the crystal structures have been determined for the first time. Single-crystal X-ray diffraction data reveal that its space groups are C2/c. The crystalline structure is constituted by K/BaO8 distorted square antiprisms, distorted LuO8 polyhedra and two kinds of distorted MoO4 tetrahedra, which form chains lying along the c-axis. Spectroscopic properties and energy transfer mechanisms are investigated by detailed analyses of emission and excitation spectra and excited-state lifetimes. The KBaLu(MoO4)3:Tb3+,Yb3+ phosphor shows dominant green emissions in the visible region, which are due to 5D4 → 7F5 transition of Tb3+ under excitation light in ultraviolet region as well as a 980 nm laser, and the CIE coordinates are close to the Society of Motion Picture and Television Engineers (SMPTE) standard values for primary green (0.310, 0.595). With the increasing temperature, the luminescence of KBaLu(MoO4)3:Tb3+,Yb3+ phosphor decreases almost linearly with the CIE coordinate variation from (0.326, 0.616) to (0.327, 0.530), which results in photoluminescence color variation from primary green to yellowish-green. The present results demonstrate the successful synthesis of a dual-mode luminescence material KBaLu(MoO4)3:Tb3+,Yb3+ phosphor with both up- and down-conversion luminescence properties; moreover, it can be used as a potential spectrum converter in display lighting and anti-counterfeiting.

tert-Butyl N-{4-[N-(4-hy-droxy-phen-yl)carbamo-yl]benz-yl}carbamate.

In the title compound, C19H22N2O4, the dihedral angle between the aromatic rings is 67.33 (2)°. In the crystal, molecules are linked through N—H⋯O and O—H⋯O hydrogen bonds, generating a two-dimensional network lying parallel to (100). As a result of the twist of the molecular skeleton and the hindrance of the tert-butyl groups, no π–π interactions exist between the aromatic rings.

Methyl 2-[2-(tert-but-oxy-carbonyl-amino)-1,3-benzothia-zole-6-carboxamido]-acetate.

In the title compound, C16H19N3O5S, the dihedral angle between the benzene ring and the carbonylamino group is 18.18 (2)°. In the crystal, molecules form centrosymmetric dimers via pairs of N—H⋯N hydrogen bonds. The dimers are connected via N—H⋯O hydrogen bonds into a three-dimensional network..

(E)-Methyl 2-[(4-nitro-phen-yl)-hydrazono]-propanoate.

The title compound, C10H11N3O4, is a condensation product of 4-nitrophenylhydrazine and methyl pyruvate. The complete molecule except for the methyl groups can be considered as a conjugated π system. All non-H atoms are approximately coplanar (r.m.s. deviation 0.117 Å). The crystal packing involves an N—H⋯O hydrogen bond and a π–π interaction between the aromatic rings, with a centroid–centroid distance of 3.617 Å.