CRYSTAL STRUCTURE OF THE COMPLEX OF MUNG BEAN TRYPSIN INHIBITOR LYSINE ACTIVE FRAGMENT WITH BOVINE TRYPSIN AT 1.8 A RESOLUTION

The structure of the complex of mung bean trypsin inhibitor lysine active fragment with bovine trypsin has been determined at a resolution of 1.8 A by A-ray crystallographic analysis and the complex model refined by restrained least-squares minimization with the data between 10 and 1.8 resolution.The current conventional R factor is 17.3%,and the model con- tains 1648 protein atoms,219 inhibitor atoms and 126 water molecules.The most prominent feature of the inhibitor fragment is that it does not contain any alpha-helices.Most of the chain fold in an irregular fashion.The seven residues of the binding segment of the inhibitor lysine active frag- ment are in specific contact with bovine trypsin.The binding interaction and geometry around the reactive site are similar to that observed in other studies of trypsin-inhibitor complexes.

Sirtuin 5:a review of structure,known inhibitors and clues for developing new inhibitors

Sirtuins(SIRTs) are nicotinamide adenine dinucleotide(NAD^+)-dependent protein deacetylases,which regulate important biological processes ranging from apoptosis,age-associated pathophysiologies,adipocyte and muscle differentiation,and energy expenditure to gluconeogenesis.Very recently,sirtuin 5(SIRT5) has received considerable attention due to that it was found to have weak deacetylase activity but strong desuccinylase,demalonylase and deglutarylase activities,and it was also found to be associated with several human diseases such as cancer,Alzheimer's disease,and Parkinson's disease.In this review,we for the first time summarized the structure characteristics,known peptide and small-molecule inhibitors of SIRT5,extracted some clues from current available information and introduced some feasible,practical in silico methods,which might be useful in further efforts to develop new SIRT5 inhibitors.

Discovery of dipeptidyl peptidase Ⅳ(DPP4) inhibitors based on a novel indole scaffold

Dipeptidyl peptidase Ⅳ（DPP4） inhibitors are proven in the treatment of type 2 diabetes.We designed and synthesized a series of novel indole compounds that selectively inhibit the activity of DPP4 over dipeptidyl peptidase 9（DPP9）（〉200 fold）.We further co-crystallized DPP4 with indole sulfonamide（compound 1） to confirm a proposed binding mode.Good metabolic stability of the indole compounds represents another positive attribute for further development.