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1zn8

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Revision as of 09:07, 20 January 2021

Human Adenine Phosphoribosyltransferase Complexed with AMP, in Space Group P1 at 1.76 A Resolution

Structural highlights

1zn8 is a 2 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
Related:	1ore, 1zn7, 1zn9
Gene:	APRT (HUMAN)
Activity:	Adenine phosphoribosyltransferase, with EC number 2.4.2.7
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[APT_HUMAN] Defects in APRT are the cause of adenine phosphoribosyltransferase deficiency (APRTD) [MIM:614723]; also known as 2,8-dihydroxyadenine urolithiasis. An enzymatic deficiency that can lead to urolithiasis and renal failure. Patients have 2,8-dihydroxyadenine (DHA) urinary stones.^[1] ^[2] ^[3] ^[4] ^[5] ^[6] ^[7] ^[8]

Function

[APT_HUMAN] Catalyzes a salvage reaction resulting in the formation of AMP, that is energically less costly than de novo synthesis.

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

Adenine phosphoribosyltransferase (APRT) is an important enzyme component of the purine recycling pathway. Parasitic protozoa of the order Kinetoplastida are unable to synthesize purines de novo and use the salvage pathway for the synthesis of purine bases rendering this biosynthetic pathway an attractive target for antiparasitic drug design. The recombinant human adenine phosphoribosyltransferase (hAPRT) structure was resolved in the presence of AMP in the active site to 1.76 A resolution and with the substrates PRPP and adenine simultaneously bound to the catalytic site to 1.83 A resolution. An additional structure was solved containing one subunit of the dimer in the apo-form to 2.10 A resolution. Comparisons of these three hAPRT structures with other 'type I' PRTases revealed several important features of this class of enzymes. Our data indicate that the flexible loop structure adopts an open conformation before and after binding of both substrates adenine and PRPP. Comparative analyses presented here provide structural evidence to propose the role of Glu104 as the residue that abstracts the proton of adenine N9 atom before its nucleophilic attack on the PRPP anomeric carbon. This work leads to new insights to the understanding of the APRT catalytic mechanism.

Structural Complexes of Human Adenine Phosphoribosyltransferase Reveal Novel Features of the APRT Catalytic Mechanism.,Silva CH, Silva M, Iulek J, Thiemann OH J Biomol Struct Dyn. 2008 Jun;25(6):589-98. PMID:18399692^[9]

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

References

↑ Chen J, Sahota A, Laxdal T, Scrine M, Bowman S, Cui C, Stambrook PJ, Tischfield JA. Identification of a single missense mutation in the adenine phosphoribosyltransferase (APRT) gene from five Icelandic patients and a British patient. Am J Hum Genet. 1991 Dec;49(6):1306-11. PMID:1746557
↑ Sahota A, Chen J, Boyadjiev SA, Gault MH, Tischfield JA. Missense mutation in the adenine phosphoribosyltransferase gene causing 2,8-dihydroxyadenine urolithiasis. Hum Mol Genet. 1994 May;3(5):817-8. PMID:7915931
↑ Hidaka Y, Palella TD, O'Toole TE, Tarle SA, Kelley WN. Human adenine phosphoribosyltransferase. Identification of allelic mutations at the nucleotide level as a cause of complete deficiency of the enzyme. J Clin Invest. 1987 Nov;80(5):1409-15. PMID:3680503 doi:http://dx.doi.org/10.1172/JCI113219
↑ Hidaka Y, Tarle SA, Fujimori S, Kamatani N, Kelley WN, Palella TD. Human adenine phosphoribosyltransferase deficiency. Demonstration of a single mutant allele common to the Japanese. J Clin Invest. 1988 Mar;81(3):945-50. PMID:3343350 doi:http://dx.doi.org/10.1172/JCI113408
↑ Kamatani N, Hakoda M, Otsuka S, Yoshikawa H, Kashiwazaki S. Only three mutations account for almost all defective alleles causing adenine phosphoribosyltransferase deficiency in Japanese patients. J Clin Invest. 1992 Jul;90(1):130-5. PMID:1353080 doi:http://dx.doi.org/10.1172/JCI115825
↑ Deng L, Yang M, Frund S, Wessel T, De Abreu RA, Tischfield JA, Sahota A. 2,8-Dihydroxyadenine urolithiasis in a patient with considerable residual adenine phosphoribosyltransferase activity in cell extracts but with mutations in both copies of APRT. Mol Genet Metab. 2001 Mar;72(3):260-4. PMID:11243733 doi:10.1006/mgme.2000.3142
↑ Taniguchi A, Tsuchida S, Kuno S, Mita M, Machida T, Ioritani N, Terai C, Yamanaka H, Kamatani N. Identification of two novel mutations in adenine phosphoribosyltransferase gene in patients with 2,8-dihydroxyadenine urolithiasis. Nucleosides Nucleotides Nucleic Acids. 2004 Oct;23(8-9):1141-5. PMID:15571218 doi:10.1081/NCN-200027393
↑ Nozue H, Kamoda T, Saitoh H, Ichikawa K, Taniguchi A. A Japanese boy with adenine phosphoribosyltransferase (APRT) deficiency caused by compound heterozygosity including a novel missense mutation in APRT gene. Acta Paediatr. 2011 Dec;100(12):e285-8. doi: 10.1111/j.1651-2227.2011.02371.x., Epub 2011 Jun 17. PMID:21635362 doi:10.1111/j.1651-2227.2011.02371.x
↑ Silva CH, Silva M, Iulek J, Thiemann OH. Structural Complexes of Human Adenine Phosphoribosyltransferase Reveal Novel Features of the APRT Catalytic Mechanism. J Biomol Struct Dyn. 2008 Jun;25(6):589-98. PMID:18399692

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1zn8"

@@ Line 1: / Line 1: @@
 ==Human Adenine Phosphoribosyltransferase Complexed with AMP, in Space Group P1 at 1.76 A Resolution==
-<StructureSection load='1zn8' size='340' side='right' caption='[[1zn8]], [[Resolution|resolution]] 1.76&Aring;' scene=''>
+<StructureSection load='1zn8' size='340' side='right'caption='[[1zn8]], [[Resolution|resolution]] 1.76&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[1zn8]] is a 2 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=1ZN8 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1ZN8 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[1zn8]] is a 2 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=1ZN8 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=1ZN8 FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=AMP:ADENOSINE+MONOPHOSPHATE'>AMP</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene></td></tr>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AMP:ADENOSINE+MONOPHOSPHATE'>AMP</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene></td></tr>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1ore|1ore]], [[1zn7|1zn7]], [[1zn9|1zn9]]</td></tr>
+<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1ore|1ore]], [[1zn7|1zn7]], [[1zn9|1zn9]]</div></td></tr>
 <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">APRT ([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/Adenine_phosphoribosyltransferase Adenine phosphoribosyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.4.2.7 2.4.2.7] </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=1zn8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1zn8 OCA], [http://pdbe.org/1zn8 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1zn8 RCSB], [http://www.ebi.ac.uk/pdbsum/1zn8 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1zn8 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=1zn8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1zn8 OCA], [http://pdbe.org/1zn8 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1zn8 RCSB], [http://www.ebi.ac.uk/pdbsum/1zn8 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1zn8 ProSAT]</span></td></tr>
 </table>
 == Disease ==
@@ Line 33: / Line 33: @@
 </div>
 <div class="pdbe-citations 1zn8" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Phosphoribosyltransferase 3D structures|Phosphoribosyltransferase 3D structures]]
 == References ==
 <references/>
@@ Line 39: / Line 42: @@
 [[Category: Adenine phosphoribosyltransferase]]
 [[Category: Human]]
+[[Category: Large Structures]]
 [[Category: Iulek, J]]
 [[Category: Silva, M]]

1zn8

From Proteopedia

Revision as of 09:07, 20 January 2021

Human Adenine Phosphoribosyltransferase Complexed with AMP, in Space Group P1 at 1.76 A Resolution

Structural highlights

Disease

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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