4h4f

Crystal structure of human chymotrypsin C (CTRC) bound to inhibitor eglin c from Hirudo medicinalis

spinqualitylabelsall models 4h4f, resolution 1.90Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4h4f is a 3 chain structure with sequence from Hirudo medicinalis and Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.9Å Ligands: PO4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease CTRC_HUMAN Hereditary chronic pancreatitis. Note=Genetic variations in CTRC can predispose to chronic pancreatitis by diminishing its protective trypsin-degrading activity. Function CTRC_HUMAN Has chymotrypsin-type protease activity and hypocalcemic activity. Publication Abstract from PubMed Human chymotrypsin C (CTRC) is a pancreatic serine protease that regulates activation and degradation of trypsinogens and procarboxypeptidases by targeting specific cleavage sites within their zymogen precursors. In cleaving these regulatory sites, which are characterized by multiple flanking acidic residues, CTRC shows substrate specificity that is distinct from that of other isoforms of chymotrypsin and elastase. Here, we report the first crystal structure of active CTRC, determined at 1.9-A resolution, revealing the structural basis for binding specificity. The structure shows human CTRC bound to the small protein protease inhibitor eglin c, which binds in a substrate-like manner filling the S6-S5' subsites of the substrate binding cleft. Significant binding affinity derives from burial of preferred hydrophobic residues at the P1, P4, and P2' positions of CTRC, although acidic P2' residues can also be accommodated by formation of an interfacial salt bridge. Acidic residues may also be specifically accommodated in the P6 position. The most unique structural feature of CTRC is a ring of intense positive electrostatic surface potential surrounding the primarily hydrophobic substrate binding site. Our results indicate that long-range electrostatic attraction toward substrates of concentrated negative charge governs substrate discrimination, which explains CTRC selectivity in regulating active digestive enzyme levels. Long-range Electrostatic Complementarity Governs Substrate Recognition by Human Chymotrypsin C, a Key Regulator of Digestive Enzyme Activation.,Batra J, Szabo A, Caulfield TR, Soares AS, Sahin-Toth M, Radisky ES J Biol Chem. 2013 Apr 5;288(14):9848-59. doi: 10.1074/jbc.M113.457382. Epub 2013 , Feb 19. PMID:23430245 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Chymotrypsin 3D structures Eglin

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