PDBsum entry 4wlm

Transferase

PDB id: 4wlm

Contents

Protein chains

286 a.a.

Ligands

SO4 ×5

Metals

_MN ×2

PDB id:

4wlm

Name:

Transferase

Title:

Crystal structure of mouse xyloside xylosyltransferase 1 complexed with manganese

Structure:

Xyloside xylosyltransferase 1. Chain: a, b. Fragment: unp residues 87-392. Synonym: udp-xylose:alpha-xyloside alpha-1,3-xylosyltransferase. Engineered: yes

Source:

Mus musculus. Mouse. Organism_taxid: 10090. Gene: xxylt1. Expressed in: homo sapiens. Expression_system_taxid: 9606

Resolution:

3.00Å R-factor: 0.233 R-free: 0.287

Authors:

H.Yu,H.Li

Key ref:

H.Yu et al. (2015). Notch-modifying xylosyltransferase structures support an SNi-like retaining mechanism. Nat Chem Biol, 11, 847-854. PubMed id: 26414444 DOI: 10.1038/nchembio.1927

Date:

07-Oct-14 Release date: 30-Sep-15

Protein chains

Q3U4G3  (XXLT1_MOUSE) -  Xyloside xylosyltransferase 1 from Mus musculus

Seq: 392 a.a.

Struc: 286 a.a.

Enzyme reactions

• Enzyme class: E.C.2.4.2.62 - xylosyl alpha-1,3-xylosyltransferase.
• Reaction: 3-O-[alpha-D-xylosyl-(1->3)-beta-D-glucosyl]-L-seryl-[EGF-like domain protein] + UDP-alpha-D-xylose = 3-O-[alpha-D-xylosyl-(1->3)-alpha-D- xylosyl-(1->3)-beta-D-glucosyl]-L-seryl-[EGF-like domain protein] + UDP + H⁺

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

Added reference

DOI no: 10.1038/nchembio.1927

Nat Chem Biol 11:847-854 (2015)

PubMed id: 26414444

Notch-modifying xylosyltransferase structures support an SNi-like retaining mechanism.

H.Yu, M.Takeuchi, J.LeBarron, J.Kantharia, E.London, H.Bakker, R.S.Haltiwanger, H.Li, H.Takeuchi.

ABSTRACT

A major question remaining in glycobiology is how a glycosyltransferase (GT) that retains the anomeric linkage of a sugar catalyzes the reaction. Xyloside α-1,3-xylosyltransferase (XXYLT1) is a retaining GT that regulates Notch receptor activation by adding xylose to the Notch extracellular domain. Here, using natural acceptor and donor substrates and active Mus musculus XXYLT1, we report a series of crystallographic snapshots along the reaction, including an unprecedented natural and competent Michaelis reaction complex for retaining enzymes. These structures strongly support the SNi-like reaction as the retaining mechanism for XXYLT1. Unexpectedly, the epidermal growth factor-like repeat acceptor substrate undergoes a large conformational change upon binding to the active site, providing a structural basis for substrate specificity. Our improved understanding of this retaining enzyme will accelerate the design of retaining GT inhibitors that can modulate Notch activity in pathological situations in which Notch dysregulation is known to cause cancer or developmental disorders.