PDBsum entry 4wmb

Transferase/protein binding

PDB id: 4wmb

Contents

Protein chains

299 a.a.

35 a.a.

Ligands

BGC-XYS

UDP

SO4

Metals

_MN

Waters ×71

PDB id:

4wmb

Name:

Transferase/protein binding

Title:

Crystal structure of mouse xyloside xylosyltransferase 1 complexed with manganese, acceptor ligand and udp

Structure:

Xyloside xylosyltransferase 1. Chain: a. Fragment: unp residues 87-392. Synonym: udp-xylose:alpha-xyloside alpha-1,3-xylosyltransferase. Engineered: yes. Coagulation factor ix. Chain: d. Fragment: unp residues 92-130. Synonym: christmas factor,plasma thromboplastin component,ptc.

Source:

Mus musculus. Mouse. Organism_taxid: 10090. Gene: xxylt1. Expressed in: homo sapiens. Expression_system_taxid: 9606. Expression_system_cell_line: hek293t. Homo sapiens. Human.

Resolution:

2.05Å R-factor: 0.202 R-free: 0.235

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:

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

Protein chain

Q3U4G3  (XXLT1_MOUSE) -  Xyloside xylosyltransferase 1 from Mus musculus

Seq: 392 a.a.

Struc: 299 a.a.

Protein chain

P00740  (FA9_HUMAN) -  Coagulation factor IX from Homo sapiens

Seq: 461 a.a.

Struc: 35 a.a.

Enzyme reactions

• Enzyme class 1: Chain A: 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⁺

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(+) (Bound ligand (Het Group name = UDP) corresponds exactly)

• Enzyme class 2: Chain D: E.C.3.4.21.22 - coagulation factor IXa.
• Reaction: Hydrolyzes one Arg-|-Ile bond in factor X to form factor Xa.

Note, where more than one E.C. class is given (as above), each may correspond to a different protein domain or, in the case of polyprotein precursors, to a different mature protein.

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.