1tqn: Difference between revisions

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New page: left|200px<br /> <applet load="1tqn" size="450" color="white" frame="true" align="right" spinBox="true" caption="1tqn, resolution 2.05Å" /> '''Crystal Structure o...
 
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[[Image:1tqn.gif|left|200px]]<br />
<applet load="1tqn" size="450" color="white" frame="true" align="right" spinBox="true"
caption="1tqn, resolution 2.05&Aring;" />
'''Crystal Structure of Human Microsomal P450 3A4'''<br />


==Overview==
==Crystal Structure of Human Microsomal P450 3A4==
The structure of P450 3A4 was determined by x-ray crystallography to, 2.05-A resolution. P450 3A4 catalyzes the metabolic clearance of a large, number of clinically used drugs, and a number of adverse drug-drug, interactions reflect the inhibition or induction of the enzyme. P450 3A4, exhibits a relatively large substrate-binding cavity that is consistent, with its capacity to oxidize bulky substrates such as cyclosporin, statins, taxanes, and macrolide antibiotics. Family 3A P450s also exhibit, unusual kinetic characteristics that suggest simultaneous occupancy by, smaller substrates. Although the active site volume is similar to that of, P450 2C8 (PDB code: 1PQ2), the shape of the active site cavity differs, considerably due to differences in the folding and packing of portions of, the protein that form the cavity. Compared with P450 2C8, the active site, cavity of 3A4 is much larger near the heme iron. The lower constraints on, the motions of small substrates near the site of oxygen activation may, diminish the efficiency of substrate oxidation, which may, in turn, be, improved by space restrictions imposed by the presence of a second, substrate molecule. The structure of P450 3A4 should facilitate a better, understanding of the substrate selectivity of the enzyme.
<StructureSection load='1tqn' size='340' side='right'caption='[[1tqn]], [[Resolution|resolution]] 2.05&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1tqn]] is a 1 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=1TQN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1TQN 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]] 2.05&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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=1tqn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1tqn OCA], [https://pdbe.org/1tqn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1tqn RCSB], [https://www.ebi.ac.uk/pdbsum/1tqn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1tqn ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/CP3A4_HUMAN CP3A4_HUMAN] Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4-hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Acts as a 1,8-cineole 2-exo-monooxygenase. The enzyme also hydroxylates etoposide.<ref>PMID:11159812</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/tq/1tqn_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=1tqn ConSurf].
<div style="clear:both"></div>


==About this Structure==
==See Also==
1TQN 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 HEM as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Unspecific_monooxygenase Unspecific monooxygenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.14.14.1 1.14.14.1] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1TQN OCA].
*[[Cytochrome P450 3D structures|Cytochrome P450 3D structures]]
 
== References ==
==Reference==
<references/>
The structure of human microsomal cytochrome P450 3A4 determined by X-ray crystallography to 2.05-A resolution., Yano JK, Wester MR, Schoch GA, Griffin KJ, Stout CD, Johnson EF, J Biol Chem. 2004 Sep 10;279(37):38091-4. Epub 2004 Jul 16. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=15258162 15258162]
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Single protein]]
[[Category: Large Structures]]
[[Category: Unspecific monooxygenase]]
[[Category: Griffin KJ]]
[[Category: Griffin, K.J.]]
[[Category: Johnson EF]]
[[Category: Johnson, E.F.]]
[[Category: Schoch GA]]
[[Category: Schoch, G.A.]]
[[Category: Stout CD]]
[[Category: Stout, C.D.]]
[[Category: Wester MR]]
[[Category: Wester, M.R.]]
[[Category: Yano JK]]
[[Category: Yano, J.K.]]
[[Category: HEM]]
[[Category: cyp3a4]]
[[Category: drug metabolizing enzyme]]
[[Category: heme]]
[[Category: monooxygenase]]
[[Category: oxidoreductase]]
[[Category: p450]]
 
''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 19:27:04 2007''

Latest revision as of 11:41, 14 February 2024

Crystal Structure of Human Microsomal P450 3A4Crystal Structure of Human Microsomal P450 3A4

Structural highlights

1tqn is a 1 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 2.05Å
Ligands:
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

CP3A4_HUMAN Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4-hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Acts as a 1,8-cineole 2-exo-monooxygenase. The enzyme also hydroxylates etoposide.[1]

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. ↑ Miyazawa M, Shindo M, Shimada T. Oxidation of 1,8-cineole, the monoterpene cyclic ether originated from eucalyptus polybractea, by cytochrome P450 3A enzymes in rat and human liver microsomes. Drug Metab Dispos. 2001 Feb;29(2):200-5. PMID:11159812

1tqn, resolution 2.05Å

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