PDBsum entry 4xwh

Hydrolase

PDB id: 4xwh

Contents

Protein chain

720 a.a.

Ligands

NAG-NAG-BMA

NAG-NAG ×2

NAG ×3

GOL ×3

XYL ×2

Waters ×279

PDB id:

4xwh

Name:

Hydrolase

Title:

Crystal structure of the human n-acetyl-alpha-glucosaminidase

Structure:

Alpha-n-acetylglucosaminidase. Chain: a. Synonym: n-acetyl-alpha-glucosaminidase,NAG. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: naglu, ufhsd1. Expressed in: homo sapiens. Expression_system_taxid: 9606. Expression_system_cell_line: ht-1080.

Resolution:

2.32Å R-factor: 0.167 R-free: 0.186

Authors:

G.Birrane,M.Meiyappan,A.Dassier

Key ref:

G.Birrane et al. (2019). Structural characterization of the α-N-acetylglucosaminidase, a key enzyme in the pathogenesis of Sanfilippo syndrome B. J Struct Biol, 205, 65-71. PubMed id: 30802506 DOI: 10.1016/j.jsb.2019.02.005

Date:

28-Jan-15 Release date: 03-Feb-16

Protein chain

P54802  (ANAG_HUMAN) -  Alpha-N-acetylglucosaminidase from Homo sapiens

Seq: 743 a.a.

Struc: 720 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

Enzyme reactions

• Enzyme class: E.C.3.2.1.50 - alpha-N-acetylglucosaminidase.
• Reaction: Hydrolysis of terminal non-reducing N-acetyl-D-glucosamine residues in N-acetyl-alpha-D-glucosaminides.

DOI no: 10.1016/j.jsb.2019.02.005

J Struct Biol 205:65-71 (2019)

PubMed id: 30802506

Structural characterization of the α-N-acetylglucosaminidase, a key enzyme in the pathogenesis of Sanfilippo syndrome B.

G.Birrane, A.L.Dassier, A.Romashko, D.Lundberg, K.Holmes, T.Cottle, A.W.Norton, B.Zhang, M.F.Concino, M.Meiyappan.

ABSTRACT

Mucopolysaccharidosis III B (MPS III-B) is a rare lysosomal storage disorder caused by deficiencies in Alpha-N-acetylglucosaminidase (NAGLU) for which there is currently no cure, and present treatment is largely supportive. Understanding the structure of NAGLU may allow for identification of novel therapeutic targets for MPS III-B. Here we describe the first crystal structure of human NAGLU, determined to a resolution of 2.3 Å. The crystal structure reveals a novel homotrimeric configuration, maintained primarily by hydrophobic and electrostatic interactions via domain II of three contiguous domains from the N- to C-terminus. The active site cleft is located between domains II and III. Catalytic glutamate residues, E316 and E446, are located at the top of the (α/β)₈ barrel structure in domain II. We utilized the three-dimensional structure of NAGLU to map several MPS III-B mutations, and hypothesize their functional consequences. Revealing atomic level structural information about this critical lysosomal enzyme paves the way for the design of novel therapeutics to target the underlying causes of MPS III-B.