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[[Image:2bwn.gif|left|200px]]<br /><applet load="2bwn" size="350" color="white" frame="true" align="right" spinBox="true"
caption="2bwn, resolution 2.10&Aring;" />
'''5-AMINOLEVULINATE SYNTHASE FROM RHODOBACTER CAPSULATUS'''<br />


==Overview==
==5-Aminolevulinate Synthase from Rhodobacter capsulatus==
5-Aminolevulinate synthase (ALAS) is the first and rate-limiting enzyme of, heme biosynthesis in humans, animals, other non-plant eukaryotes, and, alpha-proteobacteria. It catalyzes the synthesis of 5-aminolevulinic acid, the first common precursor of all tetrapyrroles, from glycine and, succinyl-coenzyme A (sCoA) in a pyridoxal 5'-phosphate (PLP)-dependent, manner. X-linked sideroblastic anemias (XLSAs), a group of severe, disorders in humans characterized by inadequate formation of heme in, erythroblast mitochondria, are caused by mutations in the gene for, erythroid eALAS, one of two human genes for ALAS. We present the first, crystal structure of homodimeric ALAS from Rhodobacter capsulatus, (ALAS(Rc)) binding its cofactor PLP. We, furthermore, present structures, of ALAS(Rc) in complex with the substrates glycine or sCoA. The sequence, identity of ALAS from R. capsulatus and human eALAS is 49%. XLSA-causing, mutations may thus be mapped, revealing the molecular basis of XLSA in, humans. Mutations are found to obstruct substrate binding, disrupt the, dimer interface, or hamper the correct folding. The structure of ALAS, completes the structural analysis of enzymes in heme biosynthesis.
<StructureSection load='2bwn' size='340' side='right'caption='[[2bwn]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2bwn]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Rhodobacter_capsulatus Rhodobacter capsulatus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2BWN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2BWN FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.1&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACY:ACETIC+ACID'>ACY</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=FMT:FORMIC+ACID'>FMT</scene>, <scene name='pdbligand=PLP:PYRIDOXAL-5-PHOSPHATE'>PLP</scene>, <scene name='pdbligand=SIN:SUCCINIC+ACID'>SIN</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></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=2bwn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2bwn OCA], [https://pdbe.org/2bwn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2bwn RCSB], [https://www.ebi.ac.uk/pdbsum/2bwn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2bwn ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/HEM1_RHOCB HEM1_RHOCB]
== 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/bw/2bwn_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=2bwn ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
5-Aminolevulinate synthase (ALAS) is the first and rate-limiting enzyme of heme biosynthesis in humans, animals, other non-plant eukaryotes, and alpha-proteobacteria. It catalyzes the synthesis of 5-aminolevulinic acid, the first common precursor of all tetrapyrroles, from glycine and succinyl-coenzyme A (sCoA) in a pyridoxal 5'-phosphate (PLP)-dependent manner. X-linked sideroblastic anemias (XLSAs), a group of severe disorders in humans characterized by inadequate formation of heme in erythroblast mitochondria, are caused by mutations in the gene for erythroid eALAS, one of two human genes for ALAS. We present the first crystal structure of homodimeric ALAS from Rhodobacter capsulatus (ALAS(Rc)) binding its cofactor PLP. We, furthermore, present structures of ALAS(Rc) in complex with the substrates glycine or sCoA. The sequence identity of ALAS from R. capsulatus and human eALAS is 49%. XLSA-causing mutations may thus be mapped, revealing the molecular basis of XLSA in humans. Mutations are found to obstruct substrate binding, disrupt the dimer interface, or hamper the correct folding. The structure of ALAS completes the structural analysis of enzymes in heme biosynthesis.


==About this Structure==
Crystal structure of 5-aminolevulinate synthase, the first enzyme of heme biosynthesis, and its link to XLSA in humans.,Astner I, Schulze JO, van den Heuvel J, Jahn D, Schubert WD, Heinz DW EMBO J. 2005 Sep 21;24(18):3166-77. Epub 2005 Aug 25. PMID:16121195<ref>PMID:16121195</ref>
2BWN is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Rhodobacter_capsulatus Rhodobacter capsulatus] with <scene name='pdbligand=CL:'>CL</scene>, <scene name='pdbligand=SO4:'>SO4</scene>, <scene name='pdbligand=SIN:'>SIN</scene>, <scene name='pdbligand=ACY:'>ACY</scene> and <scene name='pdbligand=FMT:'>FMT</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/5-aminolevulinate_synthase 5-aminolevulinate synthase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.3.1.37 2.3.1.37] Known structural/functional Site: <scene name='pdbsite=AC1:Cbx+Binding+Site+For+Chain+E'>AC1</scene>. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2BWN OCA].


==Reference==
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
Crystal structure of 5-aminolevulinate synthase, the first enzyme of heme biosynthesis, and its link to XLSA in humans., Astner I, Schulze JO, van den Heuvel J, Jahn D, Schubert WD, Heinz DW, EMBO J. 2005 Sep 21;24(18):3166-77. Epub 2005 Aug 25. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=16121195 16121195]
</div>
[[Category: 5-aminolevulinate synthase]]
<div class="pdbe-citations 2bwn" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Rhodobacter capsulatus]]
[[Category: Rhodobacter capsulatus]]
[[Category: Single protein]]
[[Category: Astner I]]
[[Category: Astner, I.]]
[[Category: Heinz DW]]
[[Category: Heinz, D.W.]]
[[Category: Jahn D]]
[[Category: Heuvel, J.J.Van.Den.]]
[[Category: Schubert W-D]]
[[Category: Jahn, D.]]
[[Category: Schulze JO]]
[[Category: Schubert, W.D.]]
[[Category: Van den Heuvel JJ]]
[[Category: Schulze, J.O.]]
[[Category: ACY]]
[[Category: CL]]
[[Category: FMT]]
[[Category: SIN]]
[[Category: SO4]]
[[Category: acyltransferase]]
[[Category: heme biosynthesis]]
[[Category: pyridoxal phosphate dependent]]
[[Category: tetrapyrrole biosynthesis]]
[[Category: transferase]]
 
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Feb  3 10:28:38 2008''

Latest revision as of 16:57, 13 December 2023

5-Aminolevulinate Synthase from Rhodobacter capsulatus5-Aminolevulinate Synthase from Rhodobacter capsulatus

Structural highlights

2bwn is a 4 chain structure with sequence from Rhodobacter capsulatus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.1Å
Ligands:, , , , ,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

HEM1_RHOCB

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

5-Aminolevulinate synthase (ALAS) is the first and rate-limiting enzyme of heme biosynthesis in humans, animals, other non-plant eukaryotes, and alpha-proteobacteria. It catalyzes the synthesis of 5-aminolevulinic acid, the first common precursor of all tetrapyrroles, from glycine and succinyl-coenzyme A (sCoA) in a pyridoxal 5'-phosphate (PLP)-dependent manner. X-linked sideroblastic anemias (XLSAs), a group of severe disorders in humans characterized by inadequate formation of heme in erythroblast mitochondria, are caused by mutations in the gene for erythroid eALAS, one of two human genes for ALAS. We present the first crystal structure of homodimeric ALAS from Rhodobacter capsulatus (ALAS(Rc)) binding its cofactor PLP. We, furthermore, present structures of ALAS(Rc) in complex with the substrates glycine or sCoA. The sequence identity of ALAS from R. capsulatus and human eALAS is 49%. XLSA-causing mutations may thus be mapped, revealing the molecular basis of XLSA in humans. Mutations are found to obstruct substrate binding, disrupt the dimer interface, or hamper the correct folding. The structure of ALAS completes the structural analysis of enzymes in heme biosynthesis.

Crystal structure of 5-aminolevulinate synthase, the first enzyme of heme biosynthesis, and its link to XLSA in humans.,Astner I, Schulze JO, van den Heuvel J, Jahn D, Schubert WD, Heinz DW EMBO J. 2005 Sep 21;24(18):3166-77. Epub 2005 Aug 25. PMID:16121195[1]

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

References

  1. ↑ Astner I, Schulze JO, van den Heuvel J, Jahn D, Schubert WD, Heinz DW. Crystal structure of 5-aminolevulinate synthase, the first enzyme of heme biosynthesis, and its link to XLSA in humans. EMBO J. 2005 Sep 21;24(18):3166-77. Epub 2005 Aug 25. PMID:16121195

2bwn, resolution 2.10Å

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