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2ger

From Proteopedia

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Current revision

Crystal Structure and Oxidative Mechanism of Human Pyrroline-5-carboxylate Reductase

Structural highlights

2ger is a 5 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Activity:	Pyrroline-5-carboxylate reductase, with EC number 1.5.1.2
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[P5CR1_HUMAN] Defects in PYCR1 are the cause of cutis laxa autosomal recessive type 2B (ARCL2B) [MIM:612940]. A multisystem disorder characterized by the appearance of premature aging, wrinkled and lax skin with reduced elasticity, joint laxity, craniofacial dysmorphic features, intrauterine growth retardation with some degree of postnatal growth deficiency, and developmental delay.^[1] ^[2] Defects in PYCR1 are the cause of cutis laxa, autosomal recessive, type 3B (ARCL3B) [MIM:614438]. ARCL3B is a disorder characterized by an aged appearance with distinctive facial features, sparse hair, ophthalmologic abnormalities, intrauterine growth retardation, and cutis laxa.^[3] ^[4]

Function

[P5CR1_HUMAN] Housekeeping enzyme that catalyzes the last step in proline biosynthesis. Can utilize both NAD and NADP, but has higher affinity for NAD. Involved in the cellular response to oxidative stress.^[5] ^[6]

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

Pyrroline-5-carboxylate reductase (P5CR) is a universal housekeeping enzyme that catalyzes the reduction of Delta(1)-pyrroline-5-carboxylate (P5C) to proline using NAD(P)H as the cofactor. The enzymatic cycle between P5C and proline is very important for the regulation of amino acid metabolism, intracellular redox potential, and apoptosis. Here, we present the 2.8 Angstroms resolution structure of the P5CR apo enzyme, its 3.1 Angstroms resolution ternary complex with NAD(P)H and substrate-analog. The refined structures demonstrate a decameric architecture with five homodimer subunits and ten catalytic sites arranged around a peripheral circular groove. Mutagenesis and kinetic studies reveal the pivotal roles of the dinucleotide-binding Rossmann motif and residue Glu221 in the human enzyme. Human P5CR is thermostable and the crystals were grown at 37 degrees C. The enzyme is implicated in oxidation of the anti-tumor drug thioproline.

Crystal structure of human pyrroline-5-carboxylate reductase.,Meng Z, Lou Z, Liu Z, Li M, Zhao X, Bartlam M, Rao Z J Mol Biol. 2006 Jun 23;359(5):1364-77. Epub 2006 May 11. PMID:16730026^[7]

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

References

↑ Reversade B, Escande-Beillard N, Dimopoulou A, Fischer B, Chng SC, Li Y, Shboul M, Tham PY, Kayserili H, Al-Gazali L, Shahwan M, Brancati F, Lee H, O'Connor BD, Schmidt-von Kegler M, Merriman B, Nelson SF, Masri A, Alkazaleh F, Guerra D, Ferrari P, Nanda A, Rajab A, Markie D, Gray M, Nelson J, Grix A, Sommer A, Savarirayan R, Janecke AR, Steichen E, Sillence D, Hausser I, Budde B, Nurnberg G, Nurnberg P, Seemann P, Kunkel D, Zambruno G, Dallapiccola B, Schuelke M, Robertson S, Hamamy H, Wollnik B, Van Maldergem L, Mundlos S, Kornak U. Mutations in PYCR1 cause cutis laxa with progeroid features. Nat Genet. 2009 Sep;41(9):1016-21. doi: 10.1038/ng.413. Epub 2009 Aug 2. PMID:19648921 doi:10.1038/ng.413
↑ Guernsey DL, Jiang H, Evans SC, Ferguson M, Matsuoka M, Nightingale M, Rideout AL, Provost S, Bedard K, Orr A, Dube MP, Ludman M, Samuels ME. Mutation in pyrroline-5-carboxylate reductase 1 gene in families with cutis laxa type 2. Am J Hum Genet. 2009 Jul;85(1):120-9. doi: 10.1016/j.ajhg.2009.06.008. Epub 2009 , Jul 2. PMID:19576563 doi:10.1016/j.ajhg.2009.06.008
↑ Reversade B, Escande-Beillard N, Dimopoulou A, Fischer B, Chng SC, Li Y, Shboul M, Tham PY, Kayserili H, Al-Gazali L, Shahwan M, Brancati F, Lee H, O'Connor BD, Schmidt-von Kegler M, Merriman B, Nelson SF, Masri A, Alkazaleh F, Guerra D, Ferrari P, Nanda A, Rajab A, Markie D, Gray M, Nelson J, Grix A, Sommer A, Savarirayan R, Janecke AR, Steichen E, Sillence D, Hausser I, Budde B, Nurnberg G, Nurnberg P, Seemann P, Kunkel D, Zambruno G, Dallapiccola B, Schuelke M, Robertson S, Hamamy H, Wollnik B, Van Maldergem L, Mundlos S, Kornak U. Mutations in PYCR1 cause cutis laxa with progeroid features. Nat Genet. 2009 Sep;41(9):1016-21. doi: 10.1038/ng.413. Epub 2009 Aug 2. PMID:19648921 doi:10.1038/ng.413
↑ Lin DS, Chang JH, Liu HL, Wei CH, Yeung CY, Ho CS, Shu CH, Chiang MF, Chuang CK, Huang YW, Wu TY, Jian YR, Huang ZD, Lin SP. Compound heterozygous mutations in PYCR1 further expand the phenotypic spectrum of De Barsy syndrome. Am J Med Genet A. 2011 Dec;155A(12):3095-9. doi: 10.1002/ajmg.a.34326. Epub 2011 , Nov 3. PMID:22052856 doi:10.1002/ajmg.a.34326
↑ Reversade B, Escande-Beillard N, Dimopoulou A, Fischer B, Chng SC, Li Y, Shboul M, Tham PY, Kayserili H, Al-Gazali L, Shahwan M, Brancati F, Lee H, O'Connor BD, Schmidt-von Kegler M, Merriman B, Nelson SF, Masri A, Alkazaleh F, Guerra D, Ferrari P, Nanda A, Rajab A, Markie D, Gray M, Nelson J, Grix A, Sommer A, Savarirayan R, Janecke AR, Steichen E, Sillence D, Hausser I, Budde B, Nurnberg G, Nurnberg P, Seemann P, Kunkel D, Zambruno G, Dallapiccola B, Schuelke M, Robertson S, Hamamy H, Wollnik B, Van Maldergem L, Mundlos S, Kornak U. Mutations in PYCR1 cause cutis laxa with progeroid features. Nat Genet. 2009 Sep;41(9):1016-21. doi: 10.1038/ng.413. Epub 2009 Aug 2. PMID:19648921 doi:10.1038/ng.413
↑ Meng Z, Lou Z, Liu Z, Li M, Zhao X, Bartlam M, Rao Z. Crystal structure of human pyrroline-5-carboxylate reductase. J Mol Biol. 2006 Jun 23;359(5):1364-77. Epub 2006 May 11. PMID:16730026 doi:10.1016/j.jmb.2006.04.053
↑ Meng Z, Lou Z, Liu Z, Li M, Zhao X, Bartlam M, Rao Z. Crystal structure of human pyrroline-5-carboxylate reductase. J Mol Biol. 2006 Jun 23;359(5):1364-77. Epub 2006 May 11. PMID:16730026 doi:10.1016/j.jmb.2006.04.053

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/2ger"

@@ Line 1: / Line 1: @@
-{{STRUCTURE_2ger|  PDB=2ger  |  SCENE=  }}
-===Crystal Structure and Oxidative Mechanism of Human Pyrroline-5-carboxylate Reductase===
-{{ABSTRACT_PUBMED_16730026}}
-==Disease==
+==Crystal Structure and Oxidative Mechanism of Human Pyrroline-5-carboxylate Reductase==
-[[http://www.uniprot.org/uniprot/P5CR1_HUMAN P5CR1_HUMAN]] Defects in PYCR1 are the cause of cutis laxa autosomal recessive type 2B (ARCL2B) [MIM:[http://omim.org/entry/612940 612940]]. A multisystem disorder characterized by the appearance of premature aging, wrinkled and lax skin with reduced elasticity, joint laxity, craniofacial dysmorphic features, intrauterine growth retardation with some degree of postnatal growth deficiency, and developmental delay.<ref>PMID:19648921</ref><ref>PMID:19576563</ref>  Defects in PYCR1 are the cause of cutis laxa, autosomal recessive, type 3B (ARCL3B) [MIM:[http://omim.org/entry/614438 614438]]. ARCL3B is a disorder characterized by an aged appearance with distinctive facial features, sparse hair, ophthalmologic abnormalities, intrauterine growth retardation, and cutis laxa.<ref>PMID:19648921</ref><ref>PMID:22052856</ref>
+<StructureSection load='2ger' size='340' side='right'caption='[[2ger]], [[Resolution|resolution]] 3.10&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[2ger]] is a 5 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2GER OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2GER FirstGlance]. <br>
+</td></tr><tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Pyrroline-5-carboxylate_reductase Pyrroline-5-carboxylate reductase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.5.1.2 1.5.1.2] </span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2ger FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ger OCA], [https://pdbe.org/2ger PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2ger RCSB], [https://www.ebi.ac.uk/pdbsum/2ger PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2ger ProSAT]</span></td></tr>
+</table>
+== Disease ==
+[[https://www.uniprot.org/uniprot/P5CR1_HUMAN P5CR1_HUMAN]] Defects in PYCR1 are the cause of cutis laxa autosomal recessive type 2B (ARCL2B) [MIM:[https://omim.org/entry/612940 612940]]. A multisystem disorder characterized by the appearance of premature aging, wrinkled and lax skin with reduced elasticity, joint laxity, craniofacial dysmorphic features, intrauterine growth retardation with some degree of postnatal growth deficiency, and developmental delay.<ref>PMID:19648921</ref> <ref>PMID:19576563</ref>   Defects in PYCR1 are the cause of cutis laxa, autosomal recessive, type 3B (ARCL3B) [MIM:[https://omim.org/entry/614438 614438]]. ARCL3B is a disorder characterized by an aged appearance with distinctive facial features, sparse hair, ophthalmologic abnormalities, intrauterine growth retardation, and cutis laxa.<ref>PMID:19648921</ref> <ref>PMID:22052856</ref>
+== Function ==
+[[https://www.uniprot.org/uniprot/P5CR1_HUMAN P5CR1_HUMAN]] Housekeeping enzyme that catalyzes the last step in proline biosynthesis. Can utilize both NAD and NADP, but has higher affinity for NAD. Involved in the cellular response to oxidative stress.<ref>PMID:19648921</ref> <ref>PMID:16730026</ref>
+== Evolutionary Conservation ==
+[[Image:Consurf_key_small.gif|200px|right]]
+Check<jmol>
+  <jmolCheckbox>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ge/2ger_consurf.spt"</scriptWhenChecked>
+    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
+    <text>to colour the structure by Evolutionary Conservation</text>
+  </jmolCheckbox>
+</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2ger ConSurf].
+<div style="clear:both"></div>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Pyrroline-5-carboxylate reductase (P5CR) is a universal housekeeping enzyme that catalyzes the reduction of Delta(1)-pyrroline-5-carboxylate (P5C) to proline using NAD(P)H as the cofactor. The enzymatic cycle between P5C and proline is very important for the regulation of amino acid metabolism, intracellular redox potential, and apoptosis. Here, we present the 2.8 Angstroms resolution structure of the P5CR apo enzyme, its 3.1 Angstroms resolution ternary complex with NAD(P)H and substrate-analog. The refined structures demonstrate a decameric architecture with five homodimer subunits and ten catalytic sites arranged around a peripheral circular groove. Mutagenesis and kinetic studies reveal the pivotal roles of the dinucleotide-binding Rossmann motif and residue Glu221 in the human enzyme. Human P5CR is thermostable and the crystals were grown at 37 degrees C. The enzyme is implicated in oxidation of the anti-tumor drug thioproline.
-==Function==
+Crystal structure of human pyrroline-5-carboxylate reductase.,Meng Z, Lou Z, Liu Z, Li M, Zhao X, Bartlam M, Rao Z J Mol Biol. 2006 Jun 23;359(5):1364-77. Epub 2006 May 11. PMID:16730026<ref>PMID:16730026</ref>
-[[http://www.uniprot.org/uniprot/P5CR1_HUMAN P5CR1_HUMAN]] Housekeeping enzyme that catalyzes the last step in proline biosynthesis. Can utilize both NAD and NADP, but has higher affinity for NAD. Involved in the cellular response to oxidative stress.<ref>PMID:19648921</ref><ref>PMID:16730026</ref>
-==About this Structure==
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[2ger]] is a 5 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=2GER OCA].
+</div>
+<div class="pdbe-citations 2ger" style="background-color:#fffaf0;"></div>
 ==See Also==
 *[[Pyrroline-5-carboxylate reductase|Pyrroline-5-carboxylate reductase]]
+== References ==
-==Reference==
+<references/>
-<ref group="xtra">PMID:016730026</ref><references group="xtra"/><references/>
+__TOC__
-[[Category: Homo sapiens]]
+</StructureSection>
+[[Category: Human]]
+[[Category: Large Structures]]
 [[Category: Pyrroline-5-carboxylate reductase]]
-[[Category: Liu, Z.]]
+[[Category: Liu, Z]]
-[[Category: Lou, Z.]]
+[[Category: Lou, Z]]
-[[Category: Meng, Z.]]
+[[Category: Meng, Z]]
-[[Category: Rao, Z.]]
+[[Category: Rao, Z]]
-[[Category: Crystal structure]]
 [[Category: Oxidative mechanism of human pyrroline-5-carboxylate]]
 [[Category: Oxidoreductase]]

2ger

From Proteopedia

Current revision

Crystal Structure and Oxidative Mechanism of Human Pyrroline-5-carboxylate Reductase

Structural highlights

Disease

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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