2013
DOI: 10.1074/jbc.m113.457382
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Long-range Electrostatic Complementarity Governs Substrate Recognition by Human Chymotrypsin C, a Key Regulator of Digestive Enzyme Activation

Abstract: Background: Chymotrypsin C (CTRC) targets specific regulatory cleavage sites within trypsinogens and procarboxypeptidases. Results: The crystal structure of CTRC reveals the structural basis of substrate specificity. Conclusion: Long-range electrostatic and hydrophobic complementarity drives CTRC association with preferred substrates. Significance: The observations reveal the mechanistic basis for CTRC selectivity in digestive enzyme activation and degradation.

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Cited by 37 publications
(36 citation statements)
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“…1). Furthermore, as we learned from the recent crystal structure of human CTRC, recognition of the calcium binding loop is governed by long range electrostatic interactions between the negatively charged substrate and positively charged surface regions on CTRC (33). These macroscopic electrostatic interactions are less favorable in the mouse, due to missing positively charged residues in Ctrc (Arg-80 and Arg-240) and negatively charged residues in mouse trypsinogens T7 (Glu-32, Asp-156, and Glu-157) and T8, T9, and T20 (Glu-79 and Glu-157) (see Fig.…”
Section: Discussionmentioning
confidence: 99%
“…1). Furthermore, as we learned from the recent crystal structure of human CTRC, recognition of the calcium binding loop is governed by long range electrostatic interactions between the negatively charged substrate and positively charged surface regions on CTRC (33). These macroscopic electrostatic interactions are less favorable in the mouse, due to missing positively charged residues in Ctrc (Arg-80 and Arg-240) and negatively charged residues in mouse trypsinogens T7 (Glu-32, Asp-156, and Glu-157) and T8, T9, and T20 (Glu-79 and Glu-157) (see Fig.…”
Section: Discussionmentioning
confidence: 99%
“…Osteoclast differentiation and maturation involves the following three steps: (1) Osteoclast precursor cells are generated from bone marrow cells in response to macrophage colonystimulating factor; (2) osteoclasts begin to differentiate from the precursor cells following stimulation by RANKL; and (3) at the later stage of differentiation, osteoclasts fuse to become multinucleated giant cells, leading to the cytoskeletal actin ring formation required for bone resorption. These processes are tightly regulated to well as elastase ⅡA, but not those of elastase Ⅰ, ⅢA, and ⅢB, where the pro-peptide is removed from the mature enzyme after tryptic activation [11,[14][15][16] . CTRC (caldecrin) is a serine protease with the characteristic charge-relayed catalytic triad (His58, Asp105, and Ser200), located in the active site cleft between the barrel structures [14][15][16] .…”
Section: Activity Of Caldecrinmentioning
confidence: 99%
“…These processes are tightly regulated to well as elastase ⅡA, but not those of elastase Ⅰ, ⅢA, and ⅢB, where the pro-peptide is removed from the mature enzyme after tryptic activation [11,[14][15][16] . CTRC (caldecrin) is a serine protease with the characteristic charge-relayed catalytic triad (His58, Asp105, and Ser200), located in the active site cleft between the barrel structures [14][15][16] . After tryptic activation, caldecrin changes its structure to a substrate-accessible catalytic cleft form.…”
Section: Activity Of Caldecrinmentioning
confidence: 99%
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