Soisson SM

References (3)

Title : Structural definition and substrate specificity of the S28 protease family: the crystal structure of human prolylcarboxypeptidase - Soisson_2010_BMC.Struct.Biol_10_16
Author(s) : Soisson SM , Patel SB , Abeywickrema PD , Byrne NJ , Diehl RE , Hall DL , Ford RE , Reid JC , Rickert KW , Shipman JM , Sharma S , Lumb KJ
Ref : BMC Struct Biol , 10 :16 , 2010
Abstract : BACKGROUND: The unique S28 family of proteases is comprised of the carboxypeptidase PRCP and the aminopeptidase DPP7. The structural basis of the different substrate specificities of the two enzymes is not understood nor has the structure of the S28 fold been described. RESULTS: The experimentally phased 2.8 A crystal structure is presented for human PRCP. PRCP contains an alpha/beta hydrolase domain harboring the catalytic Asp-His-Ser triad and a novel helical structural domain that caps the active site. Structural comparisons with prolylendopeptidase and DPP4 identify the S1 proline binding site of PRCP. A structure-based alignment with the previously undescribed structure of DPP7 illuminates the mechanism of orthogonal substrate specificity of PRCP and DPP7. PRCP has an extended active-site cleft that can accommodate proline substrates with multiple N-terminal residues. In contrast, the substrate binding groove of DPP7 is occluded by a short amino-acid insertion unique to DPP7 that creates a truncated active site selective for dipeptidyl proteolysis of N-terminal substrates. CONCLUSION: The results define the structure of the S28 family of proteases, provide the structural basis of PRCP and DPP7 substrate specificity and enable the rational design of selective PRCP modulators.
ESTHER : Soisson_2010_BMC.Struct.Biol_10_16
PubMedSearch : Soisson_2010_BMC.Struct.Biol_10_16
PubMedID: 20540760
Gene_locus related to this paper: human-PRCP

Title : Expression, purification and crystallization of human prolylcarboxypeptidase. - Abeywickrema_2010_Acta.Crystallogr.Sect.F.Struct.Biol.Cryst.Commun_66_702
Author(s) : Abeywickrema PD , Patel SB , Byrne NJ , Diehl RE , Hall DL , Ford RE , Rickert KW , Reid JC , Shipman JM , Geissler WM , Pryor KD , SinhaRoy R , Soisson SM , Lumb KJ , Sharma S
Ref : Acta Crystallographica Sect F Struct Biol Cryst Commun , 66 :702 , 2010
Abstract : Prolylcarboxypeptidase (PrCP) is a lysosomal serine carboxypeptidase that cleaves a variety of C-terminal amino acids adjacent to proline and has been implicated in diseases such as hypertension and obesity. Here, the robust production, purification and crystallization of glycosylated human PrCP from stably transformed CHO cells is described. Purified PrCP yielded crystals belonging to space group R32, with unit-cell parameters a = b = 181.14, c = 240.13 A, that diffracted to better than 2.8 A resolution.
ESTHER : Abeywickrema_2010_Acta.Crystallogr.Sect.F.Struct.Biol.Cryst.Commun_66_702
PubMedSearch : Abeywickrema_2010_Acta.Crystallogr.Sect.F.Struct.Biol.Cryst.Commun_66_702
PubMedID: 20516604
Gene_locus related to this paper: human-PRCP

Title : Discovery of a highly potent, selective, and bioavailable soluble epoxide hydrolase inhibitor with excellent ex vivo target engagement - Shen_2009_J.Med.Chem_52_5009
Author(s) : Shen HC , Ding FX , Wang S , Deng Q , Zhang X , Chen Y , Zhou G , Xu S , Chen HS , Tong X , Tong V , Mitra K , Kumar S , Tsai C , Stevenson AS , Pai LY , Alonso-Galicia M , Chen X , Soisson SM , Roy S , Zhang B , Tata JR , Berger JP , Colletti SL
Ref : Journal of Medicinal Chemistry , 52 :5009 , 2009
Abstract : 4-Substituted piperidine-derived trisubstituted ureas are reported as highly potent and selective inhibitors for sEH. The SAR outlines approaches to improve activity against sEH and reduce ion channel and CYP liability. With minimal off-target activity and a good PK profile, the benchmark 2d exhibited remarkable in vitro and ex vivo target engagement. The eutomer entA-2d also elicited vasodilation effect in rat mesenteric artery.
ESTHER : Shen_2009_J.Med.Chem_52_5009
PubMedSearch : Shen_2009_J.Med.Chem_52_5009
PubMedID: 19645482