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1fsu

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Revision as of 10:26, 18 November 2020

Crystal Structure of 4-Sulfatase (human)

Structural highlights

1fsu is a 1 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, ,
NonStd Res:
Gene:	G4S (HUMAN)
Activity:	N-acetylgalactosamine-4-sulfatase, with EC number 3.1.6.12
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[ARSB_HUMAN] Defects in ARSB are the cause of mucopolysaccharidosis type 6 (MPS6) [MIM:253200]; also known as Maroteaux-Lamy syndrome. MPS6 is an autosomal recessive lysosomal storage disease characterized by intracellular accumulation of dermatan sulfate. Clinical features can include abnormal growth, short stature, stiff joints, skeletal malformations, corneal clouding, hepatosplenomegaly, and cardiac abnormalities. A wide variation in clinical severity is observed.^[1] ^[2] ^[3] ^[4] ^[5] ^[6] ^[7] ^[8] ^[9] ^[10] Arylsulfatase B activity is defective in multiple sulfatase deficiency (MSD) [MIM:272200]. A clinically and biochemically heterogeneous disorder caused by the simultaneous impairment of all sulfatases, due to defective post-translational modification and activation. It combines features of individual sulfatase deficiencies such as metachromatic leukodystrophy, mucopolysaccharidosis, chondrodysplasia punctata, hydrocephalus, ichthyosis, neurologic deterioration and developmental delay. Note=Arylsulfatase B activity is impaired in multiple sulfatase deficiency due to mutations in SUMF1. SUMF1 mutations result in defective post-translational modification of ARSB at residue Cys-91 that is not converted to 3-oxoalanine.^[11] ^[12]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

BACKGROUND:. Sulfatases catalyze the hydrolysis of sulfuric acid esters from a wide variety of substrates including glycosaminoglycans, glycolipids and steroids. There is sufficient common sequence similarity within the class of sulfatase enzymes to indicate that they have a common structure. Deficiencies of specific lysosomal sulfatases that are involved in the degradation of glycosamino-glycans lead to rare inherited clinical disorders termed mucopolysaccharidoses. In sufferers of multiple sulfatase deficiency, all sulfatases are inactive because an essential post-translational modification of a specific active-site cysteine residue to oxo-alanine does not occur. Studies of this disorder have contributed to location and characterization of the sulfatase active site. To understand the catalytic mechanism of sulfatases, and ultimately the determinants of their substrate specificities, we have determined the structure of N-acetylgalactosamine-4-sulfatase. RESULTS:. The crystal structure of the enzyme has been solved and refined at 2.5 resolution using data recorded at both 123K and 273K. The structure has two domains, the larger of which belongs to the alpha/beta class of proteins and contains the active site. The enzyme active site in the crystals contains several hitherto undescribed features. The active-site cysteine residue, Cys91, is found as the sulfate derivative of the aldehyde species, oxo-alanine. The sulfate is bound to a previously undetected metal ion, which we have identified as calcium. The structure of a vanadate-inhibited form of the enzyme has also been solved, and this structure shows that vanadate has replaced sulfate in the active site and that the vanadate is covalently linked to the protein. Preliminary data is presented for crystals soaked in the monosaccharide N-acetylgalactosamine, the structure of which forms a product complex of the enzyme. CONCLUSIONS:. The structure of N-acetylgalactosamine-4-sulfatase reveals that residues conserved amongst the sulfatase family are involved in stabilizing the calcium ion and the sulfate ester in the active site. This suggests an archetypal fold for the family of sulfatases. A catalytic role is proposed for the post-translationally modified highly conserved cysteine residue. Despite a lack of any previously detectable sequence similarity to any protein of known structure, the large sulfatase domain that contains the active site closely resembles that of alkaline phosphatase: the calcium ion in sulfatase superposes on one of the zinc ions in alkaline phosphatase and the sulfate ester of Cys91 superposes on the phosphate ion found in the active site of alkaline phosphatase.

Structure of a human lysosomal sulfatase.,Bond CS, Clements PR, Ashby SJ, Collyer CA, Harrop SJ, Hopwood JJ, Guss JM Structure. 1997 Feb 15;5(2):277-89. PMID:9032078^[13]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Wicker G, Prill V, Brooks D, Gibson G, Hopwood J, von Figura K, Peters C. Mucopolysaccharidosis VI (Maroteaux-Lamy syndrome). An intermediate clinical phenotype caused by substitution of valine for glycine at position 137 of arylsulfatase B. J Biol Chem. 1991 Nov 15;266(32):21386-91. PMID:1718978
↑ Jin WD, Jackson CE, Desnick RJ, Schuchman EH. Mucopolysaccharidosis type VI: identification of three mutations in the arylsulfatase B gene of patients with the severe and mild phenotypes provides molecular evidence for genetic heterogeneity. Am J Hum Genet. 1992 Apr;50(4):795-800. PMID:1550123
↑ Isbrandt D, Arlt G, Brooks DA, Hopwood JJ, von Figura K, Peters C. Mucopolysaccharidosis VI (Maroteaux-Lamy syndrome): six unique arylsulfatase B gene alleles causing variable disease phenotypes. Am J Hum Genet. 1994 Mar;54(3):454-63. PMID:8116615
↑ Voskoboeva E, Isbrandt D, von Figura K, Krasnopolskaya X, Peters C. Four novel mutant alleles of the arylsulfatase B gene in two patients with intermediate form of mucopolysaccharidosis VI (Maroteaux-Lamy syndrome). Hum Genet. 1994 Mar;93(3):259-64. PMID:8125475
↑ Simonaro CM, Schuchman EH. N-acetylgalactosamine-4-sulfatase: identification of four new mutations within the conserved sulfatase region causing mucopolysaccharidosis type VI. Biochim Biophys Acta. 1995 Dec 12;1272(3):129-32. PMID:8541342
↑ Litjens T, Brooks DA, Peters C, Gibson GJ, Hopwood JJ. Identification, expression, and biochemical characterization of N-acetylgalactosamine-4-sulfatase mutations and relationship with clinical phenotype in MPS-VI patients. Am J Hum Genet. 1996 Jun;58(6):1127-34. PMID:8651289
↑ Villani GR, Balzano N, Vitale D, Saviano M, Pavone V, Di Natale P. Maroteaux-lamy syndrome: five novel mutations and their structural localization. Biochim Biophys Acta. 1999 Feb 24;1453(2):185-92. PMID:10036316
↑ Wu JY, Yang CF, Lee CC, Chang JG, Tsai FJ. A novel mutation (Q239R) identified in a Taiwan Chinese patient with type VI mucopolysaccharidosis (Maroteaux-Lamy syndrome). Hum Mutat. 2000 Apr;15(4):389-90. PMID:10738004 doi:<389::AID-HUMU31>3.0.CO;2-0 10.1002/(SICI)1098-1004(200004)15:4<389::AID-HUMU31>3.0.CO;2-0
↑ Yang CF, Wu JY, Lin SP, Tsai FJ. Mucopolysaccharidosis type VI: Report of two Taiwanese patients and identification of one novel mutation. J Formos Med Assoc. 2001 Dec;100(12):820-3. PMID:11802522
↑ Karageorgos L, Harmatz P, Simon J, Pollard A, Clements PR, Brooks DA, Hopwood JJ. Mutational analysis of mucopolysaccharidosis type VI patients undergoing a trial of enzyme replacement therapy. Hum Mutat. 2004 Mar;23(3):229-33. PMID:14974081 doi:10.1002/humu.10313
↑ Schmidt B, Selmer T, Ingendoh A, von Figura K. A novel amino acid modification in sulfatases that is defective in multiple sulfatase deficiency. Cell. 1995 Jul 28;82(2):271-8. PMID:7628016
↑ Cosma MP, Pepe S, Parenti G, Settembre C, Annunziata I, Wade-Martins R, Di Domenico C, Di Natale P, Mankad A, Cox B, Uziel G, Mancini GM, Zammarchi E, Donati MA, Kleijer WJ, Filocamo M, Carrozzo R, Carella M, Ballabio A. Molecular and functional analysis of SUMF1 mutations in multiple sulfatase deficiency. Hum Mutat. 2004 Jun;23(6):576-81. PMID:15146462 doi:10.1002/humu.20040
↑ Bond CS, Clements PR, Ashby SJ, Collyer CA, Harrop SJ, Hopwood JJ, Guss JM. Structure of a human lysosomal sulfatase. Structure. 1997 Feb 15;5(2):277-89. PMID:9032078

1 Structural highlights
2 Disease
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1fsu"

@@ Line 1: / Line 1: @@
 ==Crystal Structure of 4-Sulfatase (human)==
-<StructureSection load='1fsu' size='340' side='right' caption='[[1fsu]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
+<StructureSection load='1fsu' size='340' side='right'caption='[[1fsu]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[1fsu]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1FSU OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1FSU FirstGlance]. <br>
+<table><tr><td colspan='2'>[[1fsu]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1FSU OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=1FSU FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>
 <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=ALS:(3S)-3-(SULFOOXY)-L-SERINE'>ALS</scene></td></tr>
 <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">G4S ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
 <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/N-acetylgalactosamine-4-sulfatase N-acetylgalactosamine-4-sulfatase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.6.12 3.1.6.12] </span></td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1fsu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1fsu OCA], [http://pdbe.org/1fsu PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1fsu RCSB], [http://www.ebi.ac.uk/pdbsum/1fsu PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1fsu ProSAT]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=1fsu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1fsu OCA], [http://pdbe.org/1fsu PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1fsu RCSB], [http://www.ebi.ac.uk/pdbsum/1fsu PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1fsu ProSAT]</span></td></tr>
 </table>
 == Disease ==
@@ Line 31: / Line 31: @@
 </div>
 <div class="pdbe-citations 1fsu" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Sulfatase 3D structures|Sulfatase 3D structures]]
 == References ==
 <references/>
@@ Line 36: / Line 39: @@
 </StructureSection>
 [[Category: Human]]
+[[Category: Large Structures]]
 [[Category: N-acetylgalactosamine-4-sulfatase]]
 [[Category: Bond, C]]

1fsu

From Proteopedia

Revision as of 10:26, 18 November 2020

Crystal Structure of 4-Sulfatase (human)

Structural highlights

Disease

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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