Substrate specificity of the gastrin-amidating enzyme

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Substrate specificity of the gastrin-amidating enzyme.

As is the case with many other peptide hormones of the brain and gut, gastrin requires a carboxyl-terminal amide moiety for optimal biological activity. In the structure of progastrin, the carboxyl-terminal Phe of gastrin is followed by the sequence Gly93-Arg94-Arg95, which must be processed sequentially by an endoprotease, a carboxypeptidase, and an amidating enzyme to produce amidated bioacti...

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Gastrin-amidating enzyme in the porcine pituitary and antrum. Characterization of molecular forms and substrate specificity.

As is the case with many other peptide hormones of the brain and intestine, the formation of biologically active gastrin from a glycine-extended processing intermediate occurs via the action of a peptidylglycyl alpha-amidating monooxygenase (PAM). The observation that gastrin exists primarily as unamidated precursors in the pituitary but as amidated gastrin in the antrum prompted this study to ...

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Mutations of the PC2 substrate binding pocket alter enzyme specificity.

By taking advantage of the recently published furin structure, whose catalytic domain shares high homology with other proprotein convertases, we designed mutations in the catalytic domain of PC2, altering residues Ser206, Thr271, Asp278, ArgGlu282, AlaSer323, Leu341, Asn365, and Ser380, which are both conserved and specific to this convertase, and substituting residues specific to PC1 and/or fu...

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Membrane Allostery and Unique Hydrophobic Sites Promote Enzyme Substrate Specificity

We demonstrate that lipidomics coupled with molecular dynamics reveal unique phospholipase A2 specificity toward membrane phospholipid substrates. We discovered unexpected headgroup and acyl-chain specificity for three major human phospholipases A2. The differences between each enzyme's specificity, coupled with molecular dynamics-based structural and binding studies, revealed unique binding si...

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ژورنال

عنوان ژورنال: Journal of Biological Chemistry

سال: 1993

ISSN: 0021-9258

DOI: 10.1016/s0021-9258(18)82341-9