2nz2: Difference between revisions

Revision as of 02:21, 11 September 2015

Crystal structure of human argininosuccinate synthase in complex with aspartate and citrulline

Structural highlights

2nz2 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:	ASP, CIR, NA
Gene:	ASS1, ASS (HUMAN)
Activity:	Argininosuccinate synthase, with EC number 6.3.4.5
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum

Disease

[ASSY_HUMAN] Defects in ASS1 are the cause of citrullinemia type 1 (CTLN1) [MIM:215700]. Citrullinemia belongs to the urea cycle disorders. It is an autosomal recessive disease characterized primarily by elevated serum and urine citrulline levels. Ammonia intoxication is another manifestation. CTLN1 usually manifests in the first few days of life. Affected infants appear normal at birth, but as ammonia builds up in the body they present symptoms such as lethargy, poor feeding, vomiting, seizures and loss of consciousness. Less commonly, a milder CTLN1 form can develop later in childhood or adulthood.^[1] ^[2] ^[3] ^[4] ^[5] ^[6] ^[7] ^[8] ^[9]

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

Argininosuccinate synthetase catalyzes the transformation of citrulline and aspartate into argininosuccinate and pyrophosphate using the hydrolysis of ATP to AMP and pyrophosphate. This enzymatic process constitutes the rate-limiting step in both the urea and arginine-citrulline cycles. Previous studies have investigated the crystal structures of argininosuccinate synthetase from bacterial species. In this work, the first crystal structure of human argininosuccinate synthetase in complex with the substrates citrulline and aspartate is presented. The human enzyme is compared with structures of argininosuccinate synthetase from bacteria. In addition, the structure also provides new insights into the function of the numerous clinical mutations identified in patients with type I citrullinaemia (also known as classic citrullinaemia).

Structure of human argininosuccinate synthetase.,Karlberg T, Collins R, van den Berg S, Flores A, Hammarstrom M, Hogbom M, Holmberg Schiavone L, Uppenberg J Acta Crystallogr D Biol Crystallogr. 2008 Mar;64(Pt 3):279-86. Epub 2008, Feb 20. PMID:18323623^[10]

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

References

↑ Haberle J, Pauli S, Linnebank M, Kleijer WJ, Bakker HD, Wanders RJ, Harms E, Koch HG. Structure of the human argininosuccinate synthetase gene and an improved system for molecular diagnostics in patients with classical and mild citrullinemia. Hum Genet. 2002 Apr;110(4):327-33. Epub 2002 Mar 1. PMID:11941481 doi:10.1007/s00439-002-0686-6
↑ Kobayashi K, Jackson MJ, Tick DB, O'Brien WE, Beaudet AL. Heterogeneity of mutations in argininosuccinate synthetase causing human citrullinemia. J Biol Chem. 1990 Jul 5;265(19):11361-7. PMID:2358466
↑ Kobayashi K, Rosenbloom C, Beaudet AL, O'Brien WE. Additional mutations in argininosuccinate synthetase causing citrullinemia. Mol Biol Med. 1991 Feb;8(1):95-100. PMID:1943692
↑ Kobayashi K, Shaheen N, Terazono H, Saheki T. Mutations in argininosuccinate synthetase mRNA of Japanese patients, causing classical citrullinemia. Am J Hum Genet. 1994 Dec;55(6):1103-12. PMID:7977368
↑ Shaheen N, Kobayashi K, Terazono H, Fukushige T, Horiuchi M, Saheki T. Characterization of human wild-type and mutant argininosuccinate synthetase proteins expressed in bacterial cells. Enzyme Protein. 1994-1995;48(5-6):251-64. PMID:8792870
↑ Vilaseca MA, Kobayashi K, Briones P, Lambruschini N, Campistol J, Tabata A, Alomar A, Rodes M, Lluch M, Saheki T. Phenotype and genotype heterogeneity in Mediterranean citrullinemia. Mol Genet Metab. 2001 Nov;74(3):396-8. PMID:11708871 doi:10.1006/mgme.2001.3221
↑ Gao HZ, Kobayashi K, Tabata A, Tsuge H, Iijima M, Yasuda T, Kalkanoglu HS, Dursun A, Tokatli A, Coskun T, Trefz FK, Skladal D, Mandel H, Seidel J, Kodama S, Shirane S, Ichida T, Makino S, Yoshino M, Kang JH, Mizuguchi M, Barshop BA, Fuchinoue S, Seneca S, Zeesman S, Knerr I, Rodes M, Wasant P, Yoshida I, De Meirleir L, Abdul Jalil M, Begum L, Horiuchi M, Katunuma N, Nakagawa S, Saheki T. Identification of 16 novel mutations in the argininosuccinate synthetase gene and genotype-phenotype correlation in 38 classical citrullinemia patients. Hum Mutat. 2003 Jul;22(1):24-34. PMID:12815590 doi:10.1002/humu.10230
↑ Haberle J, Pauli S, Schmidt E, Schulze-Eilfing B, Berning C, Koch HG. Mild citrullinemia in Caucasians is an allelic variant of argininosuccinate synthetase deficiency (citrullinemia type 1). Mol Genet Metab. 2003 Nov;80(3):302-6. PMID:14680976 doi:10.1016/j.ymgme.2003.08.002
↑ Kleijer WJ, Garritsen VH, van der Sterre ML, Berning C, Haberle J, Huijmans JG. Prenatal diagnosis of citrullinemia and argininosuccinic aciduria: evidence for a transmission ratio distortion in citrullinemia. Prenat Diagn. 2006 Mar;26(3):242-7. PMID:16475226 doi:10.1002/pd.1390
↑ Karlberg T, Collins R, van den Berg S, Flores A, Hammarstrom M, Hogbom M, Holmberg Schiavone L, Uppenberg J. Structure of human argininosuccinate synthetase. Acta Crystallogr D Biol Crystallogr. 2008 Mar;64(Pt 3):279-86. Epub 2008, Feb 20. PMID:18323623 doi:https://dx.doi.org/S0907444907067455

Proteopedia Page Contributors and Editors (what is this?)

OCA

[1] Haberle J, Pauli S, Linnebank M, Kleijer WJ, Bakker HD, Wanders RJ, Harms E, Koch HG. Structure of the human argininosuccinate synthetase gene and an improved system for molecular diagnostics in patients with classical and mild citrullinemia. Hum Genet. 2002 Apr;110(4):327-33. Epub 2002 Mar 1. PMID:11941481 doi:10.1007/s00439-002-0686-6

[2] Kobayashi K, Jackson MJ, Tick DB, O'Brien WE, Beaudet AL. Heterogeneity of mutations in argininosuccinate synthetase causing human citrullinemia. J Biol Chem. 1990 Jul 5;265(19):11361-7. PMID:2358466

[3] Kobayashi K, Rosenbloom C, Beaudet AL, O'Brien WE. Additional mutations in argininosuccinate synthetase causing citrullinemia. Mol Biol Med. 1991 Feb;8(1):95-100. PMID:1943692

[4] Kobayashi K, Shaheen N, Terazono H, Saheki T. Mutations in argininosuccinate synthetase mRNA of Japanese patients, causing classical citrullinemia. Am J Hum Genet. 1994 Dec;55(6):1103-12. PMID:7977368

[5] Shaheen N, Kobayashi K, Terazono H, Fukushige T, Horiuchi M, Saheki T. Characterization of human wild-type and mutant argininosuccinate synthetase proteins expressed in bacterial cells. Enzyme Protein. 1994-1995;48(5-6):251-64. PMID:8792870

[6] Vilaseca MA, Kobayashi K, Briones P, Lambruschini N, Campistol J, Tabata A, Alomar A, Rodes M, Lluch M, Saheki T. Phenotype and genotype heterogeneity in Mediterranean citrullinemia. Mol Genet Metab. 2001 Nov;74(3):396-8. PMID:11708871 doi:10.1006/mgme.2001.3221

[7] Gao HZ, Kobayashi K, Tabata A, Tsuge H, Iijima M, Yasuda T, Kalkanoglu HS, Dursun A, Tokatli A, Coskun T, Trefz FK, Skladal D, Mandel H, Seidel J, Kodama S, Shirane S, Ichida T, Makino S, Yoshino M, Kang JH, Mizuguchi M, Barshop BA, Fuchinoue S, Seneca S, Zeesman S, Knerr I, Rodes M, Wasant P, Yoshida I, De Meirleir L, Abdul Jalil M, Begum L, Horiuchi M, Katunuma N, Nakagawa S, Saheki T. Identification of 16 novel mutations in the argininosuccinate synthetase gene and genotype-phenotype correlation in 38 classical citrullinemia patients. Hum Mutat. 2003 Jul;22(1):24-34. PMID:12815590 doi:10.1002/humu.10230

[8] Haberle J, Pauli S, Schmidt E, Schulze-Eilfing B, Berning C, Koch HG. Mild citrullinemia in Caucasians is an allelic variant of argininosuccinate synthetase deficiency (citrullinemia type 1). Mol Genet Metab. 2003 Nov;80(3):302-6. PMID:14680976 doi:10.1016/j.ymgme.2003.08.002

[9] Kleijer WJ, Garritsen VH, van der Sterre ML, Berning C, Haberle J, Huijmans JG. Prenatal diagnosis of citrullinemia and argininosuccinic aciduria: evidence for a transmission ratio distortion in citrullinemia. Prenat Diagn. 2006 Mar;26(3):242-7. PMID:16475226 doi:10.1002/pd.1390

[10] Karlberg T, Collins R, van den Berg S, Flores A, Hammarstrom M, Hogbom M, Holmberg Schiavone L, Uppenberg J. Structure of human argininosuccinate synthetase. Acta Crystallogr D Biol Crystallogr. 2008 Mar;64(Pt 3):279-86. Epub 2008, Feb 20. PMID:18323623 doi:https://dx.doi.org/S0907444907067455

[1]

[2]

[3]

[4]

[5]

[6]

[7]

[8]

[9]

[10]

@@ Line 2: / Line 2: @@
 <StructureSection load='2nz2' size='340' side='right' caption='[[2nz2]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[2nz2]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2NZ2 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2NZ2 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[2nz2]] 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=2NZ2 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2NZ2 FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ASP:ASPARTIC+ACID'>ASP</scene>, <scene name='pdbligand=CIR:CITRULLINE'>CIR</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ASS1, ASS ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ASS1, ASS ([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/Argininosuccinate_synthase Argininosuccinate synthase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=6.3.4.5 6.3.4.5] </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=2nz2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2nz2 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2nz2 RCSB], [http://www.ebi.ac.uk/pdbsum/2nz2 PDBsum]</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=2nz2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2nz2 OCA], [http://pdbe.org/2nz2 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2nz2 RCSB], [http://www.ebi.ac.uk/pdbsum/2nz2 PDBsum]</span></td></tr>
 </table>
 == Disease ==
@@ Line 28: / Line 28: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 2nz2" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>
@@ Line 33: / Line 34: @@
 </StructureSection>
 [[Category: Argininosuccinate synthase]]
-[[Category: Homo sapiens]]
+[[Category: Human]]
 [[Category: Arrowsmith, C]]
 [[Category: Berg, S Van Den]]

2nz2: Difference between revisions

Revision as of 02:21, 11 September 2015

Crystal structure of human argininosuccinate synthase in complex with aspartate and citrulline

Structural highlights

Disease

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Navigation menu

Page actions

Page actions

Personal tools

Navigation

Search

Tools