1n3u: Difference between revisions

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New page: left|200px<br /> <applet load="1n3u" size="450" color="white" frame="true" align="right" spinBox="true" caption="1n3u, resolution 2.58Å" /> '''Crystal structure o...
 
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[[Image:1n3u.gif|left|200px]]<br />
<applet load="1n3u" size="450" color="white" frame="true" align="right" spinBox="true"
caption="1n3u, resolution 2.58&Aring;" />
'''Crystal structure of human heme oxygenase 1 (HO-1) in complex with its substrate heme, crystal form B'''<br />


==Overview==
==Crystal structure of human heme oxygenase 1 (HO-1) in complex with its substrate heme, crystal form B==
Heme oxygenase (HO) catalyzes the degradation of heme to biliverdin. The, crystal structure of human HO-1 in complex with heme reveals a novel, helical structure with conserved glycines in the distal helix, providing, flexibility to accommodate substrate binding and product release, (Schuller, D. J., Wilks, A., Ortiz de Montellano, P. R., and Poulos, T. L., (1999) Nat. Struct. Biol. 6, 860-867). To structurally understand the HO, catalytic pathway in more detail, we have determined the crystal structure, of human apo-HO-1 at 2.1 A and a higher resolution structure of human HO-1, in complex with heme at 1.5 A. Although the 1.5-A heme.HO-1 model confirms, our initial analysis based on the 2.08-A model, the higher resolution, structure has revealed important new details such as a solvent H-bonded, network in the active site that may be important for catalysis. Because of, the absence of the heme, the distal and proximal helices that bracket the, heme plane in the holo structure move farther apart in the apo structure, thus increasing the size of the active-site pocket. Nevertheless, the, relative positioning and conformation of critical catalytic residues, remain unchanged in the apo structure compared with the holo structure, but an important solvent H-bonded network is missing in the apoenzyme. It, thus appears that the binding of heme and a tightening of the structure, around the heme stabilize the solvent H-bonded network required for proper, catalysis.
<StructureSection load='1n3u' size='340' side='right'caption='[[1n3u]], [[Resolution|resolution]] 2.58&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1n3u]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1N3U OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1N3U 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]] 2.58&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</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=1n3u FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1n3u OCA], [https://pdbe.org/1n3u PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1n3u RCSB], [https://www.ebi.ac.uk/pdbsum/1n3u PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1n3u ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/HMOX1_HUMAN HMOX1_HUMAN] Defects in HMOX1 are the cause of heme oxygenase 1 deficiency (HMOX1D) [MIM:[https://omim.org/entry/614034 614034]. A disease characterized by impaired stress hematopoiesis, resulting in marked erythrocyte fragmentation and intravascular hemolysis, coagulation abnormalities, endothelial damage, and iron deposition in renal and hepatic tissues. Clinical features include persistent hemolytic anemia, asplenia, nephritis, generalized erythematous rash, growth retardation and hepatomegaly.<ref>PMID:9884342</ref>
== Function ==
[https://www.uniprot.org/uniprot/HMOX1_HUMAN HMOX1_HUMAN] Heme oxygenase cleaves the heme ring at the alpha methene bridge to form biliverdin. Biliverdin is subsequently converted to bilirubin by biliverdin reductase. Under physiological conditions, the activity of heme oxygenase is highest in the spleen, where senescent erythrocytes are sequestrated and destroyed.
== 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/n3/1n3u_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=1n3u ConSurf].
<div style="clear:both"></div>


==Disease==
==See Also==
Known diseases associated with this structure: Epiphyseal dysplasia, multiple, 5 OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=602109 602109]], Heme oxygenase-1 deficiency OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=141250 141250]], Osteoarthritis, hand, susceptibility to OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=602109 602109]], Spondyloepimetaphyseal dysplasia OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=602109 602109]]
*[[Heme oxygenase 3D structures|Heme oxygenase 3D structures]]
 
== References ==
==About this Structure==
<references/>
1N3U is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with CL and HEM as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Heme_oxygenase Heme oxygenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.14.99.3 1.14.99.3] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1N3U OCA].
__TOC__
 
</StructureSection>
==Reference==
Comparison of the heme-free and -bound crystal structures of human heme oxygenase-1., Lad L, Schuller DJ, Shimizu H, Friedman J, Li H, Ortiz de Montellano PR, Poulos TL, J Biol Chem. 2003 Mar 7;278(10):7834-43. Epub 2002 Dec 24. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=12500973 12500973]
[[Category: Heme oxygenase]]
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Single protein]]
[[Category: Large Structures]]
[[Category: Friedman, J.P.]]
[[Category: Friedman JP]]
[[Category: Lad, L.]]
[[Category: Lad L]]
[[Category: Li, H.]]
[[Category: Li H]]
[[Category: Montellano, P.R.Ortiz.de.]]
[[Category: Ortiz de Montellano PR]]
[[Category: Poulos, T.L.]]
[[Category: Poulos TL]]
[[Category: Schuller, D.J.]]
[[Category: Schuller DJ]]
[[Category: CL]]
[[Category: HEM]]
[[Category: alpha helices]]
[[Category: heme-binding site]]
 
''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 18:17:27 2007''

Latest revision as of 10:52, 14 February 2024

Crystal structure of human heme oxygenase 1 (HO-1) in complex with its substrate heme, crystal form BCrystal structure of human heme oxygenase 1 (HO-1) in complex with its substrate heme, crystal form B

Structural highlights

1n3u is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.58Å
Ligands:,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

HMOX1_HUMAN Defects in HMOX1 are the cause of heme oxygenase 1 deficiency (HMOX1D) [MIM:614034. A disease characterized by impaired stress hematopoiesis, resulting in marked erythrocyte fragmentation and intravascular hemolysis, coagulation abnormalities, endothelial damage, and iron deposition in renal and hepatic tissues. Clinical features include persistent hemolytic anemia, asplenia, nephritis, generalized erythematous rash, growth retardation and hepatomegaly.[1]

Function

HMOX1_HUMAN Heme oxygenase cleaves the heme ring at the alpha methene bridge to form biliverdin. Biliverdin is subsequently converted to bilirubin by biliverdin reductase. Under physiological conditions, the activity of heme oxygenase is highest in the spleen, where senescent erythrocytes are sequestrated and destroyed.

Evolutionary Conservation

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

See Also

References

  1. ↑ Yachie A, Niida Y, Wada T, Igarashi N, Kaneda H, Toma T, Ohta K, Kasahara Y, Koizumi S. Oxidative stress causes enhanced endothelial cell injury in human heme oxygenase-1 deficiency. J Clin Invest. 1999 Jan;103(1):129-35. PMID:9884342 doi:10.1172/JCI4165

1n3u, resolution 2.58Å

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