7rep: Difference between revisions
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7rep FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7rep OCA], [https://pdbe.org/7rep PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7rep RCSB], [https://www.ebi.ac.uk/pdbsum/7rep PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7rep ProSAT]</span></td></tr> | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7rep FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7rep OCA], [https://pdbe.org/7rep PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7rep RCSB], [https://www.ebi.ac.uk/pdbsum/7rep PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7rep ProSAT]</span></td></tr> | ||
</table> | </table> | ||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The emergence of new therapeutic modalities requires complementary tools for their efficient syntheses. Availability of methodologies for site-selective modification of biomolecules remains a long-standing challenge, given the inherent complexity and the presence of repeating residues that bear functional groups with similar reactivity profiles. We describe a bioconjugation strategy for modification of native peptides relying on high site selectivity conveyed by enzymes. We engineered penicillin G acylases to distinguish among free amino moieties of insulin (two at amino termini and an internal lysine) and manipulate cleavable phenylacetamide groups in a programmable manner to form protected insulin derivatives. This enables selective and specific chemical ligation to synthesize homogeneous bioconjugates, improving yield and purity compared to the existing methods, and generally opens avenues in the functionalization of native proteins to access biological probes or drugs. | |||
A chemoenzymatic strategy for site-selective functionalization of native peptides and proteins.,Fryszkowska A, An C, Alvizo O, Banerjee G, Canada KA, Cao Y, DeMong D, Devine PN, Duan D, Elgart DM, Farasat I, Gauthier DR, Guidry EN, Jia X, Kong J, Kruse N, Lexa KW, Makarov AA, Mann BF, Milczek EM, Mitchell V, Nazor J, Neri C, Orr RK, Orth P, Phillips EM, Riggins JN, Schafer WA, Silverman SM, Strulson CA, Subramanian N, Voladri R, Yang H, Yang J, Yi X, Zhang X, Zhong W Science. 2022 Jun 17;376(6599):1321-1327. doi: 10.1126/science.abn2009. Epub 2022, Jun 16. PMID:35709255<ref>PMID:35709255</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 7rep" style="background-color:#fffaf0;"></div> | |||
==See Also== | ==See Also== | ||
*[[Penicillin acylase|Penicillin acylase]] | *[[Penicillin acylase|Penicillin acylase]] | ||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
Revision as of 19:24, 6 July 2022
Crystal structure of an engineered variant of single-chain Penicillin G Acylase from Kluyvera cryocrescens (A1-Ac Rd3CHis)Crystal structure of an engineered variant of single-chain Penicillin G Acylase from Kluyvera cryocrescens (A1-Ac Rd3CHis)
Structural highlights
Publication Abstract from PubMedThe emergence of new therapeutic modalities requires complementary tools for their efficient syntheses. Availability of methodologies for site-selective modification of biomolecules remains a long-standing challenge, given the inherent complexity and the presence of repeating residues that bear functional groups with similar reactivity profiles. We describe a bioconjugation strategy for modification of native peptides relying on high site selectivity conveyed by enzymes. We engineered penicillin G acylases to distinguish among free amino moieties of insulin (two at amino termini and an internal lysine) and manipulate cleavable phenylacetamide groups in a programmable manner to form protected insulin derivatives. This enables selective and specific chemical ligation to synthesize homogeneous bioconjugates, improving yield and purity compared to the existing methods, and generally opens avenues in the functionalization of native proteins to access biological probes or drugs. A chemoenzymatic strategy for site-selective functionalization of native peptides and proteins.,Fryszkowska A, An C, Alvizo O, Banerjee G, Canada KA, Cao Y, DeMong D, Devine PN, Duan D, Elgart DM, Farasat I, Gauthier DR, Guidry EN, Jia X, Kong J, Kruse N, Lexa KW, Makarov AA, Mann BF, Milczek EM, Mitchell V, Nazor J, Neri C, Orr RK, Orth P, Phillips EM, Riggins JN, Schafer WA, Silverman SM, Strulson CA, Subramanian N, Voladri R, Yang H, Yang J, Yi X, Zhang X, Zhong W Science. 2022 Jun 17;376(6599):1321-1327. doi: 10.1126/science.abn2009. Epub 2022, Jun 16. PMID:35709255[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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