PDBsum entry 1n2k

Hydrolase

PDB id

1n2k

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Contents

			Protein chain

					482 a.a. *

			Ligands

					NAG-NAG


					NAG

			Metals

					_CA

			Waters ×48

* Residue conservation analysis

PDB id:

1n2k

Links

Name:

Hydrolase

Title:

Crystal structure of a covalent intermediate of endogenous human arylsulfatase a

Structure:

Arylsulfatase a. Chain: a. Synonym: asa, cerebroside-3-sulfate-sulfatase. Ec: 3.1.6.8

Source:

Homo sapiens. Human. Organism_taxid: 9606. Organ: placenta. Cellular_location: lysosome

Resolution:

2.75Å

R-factor:

0.202

R-free:

0.239

Authors:

M.Chruszcz,P.Laidler,M.Monkiewicz,E.Ortlund,L.Lebioda,K.Lewinski

Key ref:

M.Chruszcz et al. (2003). Crystal structure of a covalent intermediate of endogenous human arylsulfatase A. J Inorg Biochem, 96, 386-392. PubMed id: 12888274 DOI: 10.1016/S0162-0134(03)00176-4

Date:

23-Oct-02

Release date:

23-Dec-03

PROCHECK

	Headers

	References

Protein chain

P15289 (ARSA_HUMAN) - Arylsulfatase A from Homo sapiens

Seq: Struc:					507 a.a. 482 a.a.*

Key:

PfamA domain

Secondary structure

CATH domain

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



		Enzyme reactions

Enzyme class:

E.C.3.1.6.8 - cerebroside-sulfatase.

[IntEnz] [ExPASy] [KEGG] [BRENDA]

Reaction:

an N-acyl-1-beta-D-(3-O-sulfo)-galactosyl-sphing-4-enine + H2O = a beta- D-galactosyl-(1<->1')-N-acylsphing-4-enine + sulfate + H⁺

N-acyl-1-beta-D-(3-O-sulfo)-galactosyl-sphing-4-enine	+	H2O	=	beta- D-galactosyl-(1<->1')-N-acylsphing-4-enine	+	sulfate	+	H(+)

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

Key reference

DOI no: 10.1016/S0162-0134(03)00176-4	J Inorg Biochem 96:386-392 (2003)
PubMed id: 12888274

Crystal structure of a covalent intermediate of endogenous human arylsulfatase A.
M.Chruszcz, P.Laidler, M.Monkiewicz, E.Ortlund, L.Lebioda, K.Lewinski.

ABSTRACT

The structures of human arylsulfatase A crystals soaked in solutions containing 4-methylumbelliferyl phosphate and O-phospho-DL-tyrosine have been determined at 2.7- and 3.2-A resolution, respectively. The formylglycine in position 69, a residue crucial for catalytic activity, was unambiguously identified in both structures as forming a covalent bond to the phosphate moiety. A hydroxyl group is present at the Cbeta of residue 69 and the formation of one out of two possible stereomeric forms is strongly favoured. The structures confirm the importance of the gem-diol intermediate in the arylsulfatase's catalytic mechanism. The presence of an apparently stable covalent bond is consistent with the weak phosphatase activity observed for human arylsulfatase A. The structures of the complexes suggest that phosphate ions and phosphate esters inhibit arylsulfatase in non-covalent and covalent modes, respectively. The metal ion present in the active site of arylsulfatase A isolated from human placenta is Ca(2+) and not Mg(2+) as was found in the structure of the recombinant enzyme.

Literature references that cite this PDB file's key reference

PubMed id

Reference

21139846

Y.Kashman, A.Bishara, and M.Aknin (2010).
Recent N-atom containing compounds from indo-pacific invertebrates.

Mar Drugs, 8, 2810-2836.

19381802

M.Schenk, C.A.Koppisetty, D.C.Santos, E.Carmona, S.Bhatia, P.G.Nyholm, and N.Tanphaichitr (2009).
Interaction of arylsulfatase-A (ASA) with its natural sulfoglycolipid substrates: a computational and site-directed mutagenesis study.

Glycoconj J, 26, 1029-1045.

19790257

T.S.Kang, and R.C.Stevens (2009).
Structural aspects of therapeutic enzymes to treat metabolic disorders.

Hum Mutat, 30, 1591-1610.

18283100

M.A.Frese, S.Schulz, and T.Dierks (2008).
Arylsulfatase G, a novel lysosomal sulfatase.

J Biol Chem, 283, 11388-11395.

16899453

R.L.Felts, T.J.Reilly, and J.J.Tanner (2006).
Structure of Francisella tularensis AcpA: prototype of a unique superfamily of acid phosphatases and phospholipases C.

J Biol Chem, 281, 30289-30298.

PDB code:

2d1g

15634687

C.Lingwood, M.Mylvaganam, F.Minhas, B.Binnington, D.R.Branch, and R.Pomès (2005).
The sulfogalactose moiety of sulfoglycosphingolipids serves as a mimic of tyrosine phosphate in many recognition processes. Prediction and demonstration of Src homology 2 domain/sulfogalactose binding.

J Biol Chem, 280, 12542-12547.

15493058

S.R.Hanson, M.D.Best, and C.H.Wong (2004).
Sulfatases: structure, mechanism, biological activity, inhibition, and synthetic utility.

Angew Chem Int Ed Engl, 43, 5736-5763.

The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB code is shown on the right.