6PXU

Crystal structure of human GalNAc-T12 bound to a diglycosylated peptide, Mn2+, and UDP

6PXU の概要

• エントリーDOI: 10.2210/pdb6pxu/pdb
• 分子名称: Polypeptide N-acetylgalactosaminyltransferase 12, GAGATGAGAGYYITPRTGAGA, URIDINE-5'-DIPHOSPHATE, ... (8 entities in total)
• 機能のキーワード: galnac-t, mucin-type o-glycosylation, enzyme catalysis, substrate selectivity, colorectal cancer, crc, transferase
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 132554.37

構造登録者

Samara, N.L.,Fernandez, A.J. (登録日: 2019-07-27, 公開日: 2019-09-25, 最終更新日: 2024-11-06)

主引用文献

Fernandez, A.J.,Daniel, E.J.P.,Mahajan, S.P.,Gray, J.J.,Gerken, T.A.,Tabak, L.A.,Samara, N.L.
The structure of the colorectal cancer-associated enzyme GalNAc-T12 reveals how nonconserved residues dictate its function.
Proc.Natl.Acad.Sci.USA, 116:20404-20410, 2019

PubMed Abstract: Polypeptide acetylgalactosaminyl transferases (GalNAc-Ts) initiate mucin type -glycosylation by catalyzing the transfer of -acetylgalactosamine (GalNAc) to Ser or Thr on a protein substrate. Inactive and partially active variants of the isoenzyme GalNAc-T12 are present in subsets of patients with colorectal cancer, and several of these variants alter nonconserved residues with unknown functions. While previous biochemical studies have demonstrated that GalNAc-T12 selects for peptide and glycopeptide substrates through unique interactions with its catalytic and lectin domains, the molecular basis for this distinct substrate selectivity remains elusive. Here we examine the molecular basis of the activity and substrate selectivity of GalNAc-T12. The X-ray crystal structure of GalNAc-T12 in complex with a di-glycosylated peptide substrate reveals how a nonconserved GalNAc binding pocket in the GalNAc-T12 catalytic domain dictates its unique substrate selectivity. In addition, the structure provides insight into how colorectal cancer mutations disrupt the activity of GalNAc-T12 and illustrates how the rules dictating GalNAc-T12 function are distinct from those for other GalNAc-Ts.

PubMed: 31548401
DOI: 10.1073/pnas.1902211116

実験手法

X-RAY DIFFRACTION (2.007 Å)