This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.

Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.


3r1a

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Current revision (12:06, 14 March 2024) (edit) (undo)
 
(2 intermediate revisions not shown.)
Line 1: Line 1:
 +
==Closed crystal structure of cytochrome P450 2B4 covalently bound to the mechanism-based inactivator tert-butylphenylacetylene==
==Closed crystal structure of cytochrome P450 2B4 covalently bound to the mechanism-based inactivator tert-butylphenylacetylene==
-
<StructureSection load='3r1a' size='340' side='right' caption='[[3r1a]], [[Resolution|resolution]] 3.50&Aring;' scene=''>
+
<StructureSection load='3r1a' size='340' side='right'caption='[[3r1a]], [[Resolution|resolution]] 3.50&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
-
<table><tr><td colspan='2'>[[3r1a]] is a 8 chain structure with sequence from [http://en.wikipedia.org/wiki/Oryctolagus_cuniculus Oryctolagus cuniculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3R1A OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3R1A FirstGlance]. <br>
+
<table><tr><td colspan='2'>[[3r1a]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Oryctolagus_cuniculus Oryctolagus cuniculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3R1A OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3R1A FirstGlance]. <br>
-
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=TB2:(4-TERT-BUTYLPHENYL)ACETALDEHYDE'>TB2</scene></td></tr>
+
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.5&#8491;</td></tr>
-
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3r1b|3r1b]]</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>, <scene name='pdbligand=TB2:(4-TERT-BUTYLPHENYL)ACETALDEHYDE'>TB2</scene></td></tr>
-
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CYP2B4 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9986 Oryctolagus cuniculus])</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=3r1a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3r1a OCA], [https://pdbe.org/3r1a PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3r1a RCSB], [https://www.ebi.ac.uk/pdbsum/3r1a PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3r1a ProSAT]</span></td></tr>
-
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[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] </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=3r1a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3r1a OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3r1a RCSB], [http://www.ebi.ac.uk/pdbsum/3r1a PDBsum]</span></td></tr>
+
</table>
</table>
== Function ==
== Function ==
-
[[http://www.uniprot.org/uniprot/CP2B4_RABIT CP2B4_RABIT]] Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. In the epoxidation of arachidonic acid it has a unique preference for the 5,6-olefin.
+
[https://www.uniprot.org/uniprot/CP2B4_RABIT CP2B4_RABIT] Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. In the epoxidation of arachidonic acid it has a unique preference for the 5,6-olefin.
-
<div style="background-color:#fffaf0;">
+
-
== Publication Abstract from PubMed ==
+
-
A combined structural and computational analysis of rabbit cytochrome P450 2B4 covalently bound to the mechanism-based inactivator tert-butylphenylacetylene (tBPA) has yielded insight into how the enzyme retains partial activity. Since conjugation to tBPA modifies a highly conserved active site residue, the residual activity of tBPA-labeled 2B4 observed in previous studies was puzzling. Here we describe the first crystal structures of a modified mammalian P450, which show an oxygenated metabolite of tBPA conjugated to Thr 302 of helix I. These results are consistent with previous studies that identified Thr 302 as the site of conjugation. In each structure, the core of 2B4 remains unchanged, but the arrangement of plastic regions differs. This results in one structure that is compact and closed. In this conformation, tBPA points toward helix B', making a 31 degrees angle with the heme plane. This conformation is in agreement with previously performed in silico experiments. However, dimerization of 2B4 in the other structure, which is caused by movement of the B/C loop and helices F through G, alters the position of tBPA. In this case, tBPA lies almost parallel to the heme plane due to the presence of helix F' of the opposite monomer entering the active site to stabilize the dimer. However, docking experiments using this open form show that tBPA is able to rotate upward to give testosterone and 7-ethoxy-4-trifluoromethylcoumarin access to the heme, which could explain the previously observed partial activity.
+
-
 
+
-
Structural Analysis of Mammalian Cytochrome P450 2B4 Covalently Bound to the Mechanism-Based Inactivator tert-Butylphenylacetylene: Insight into Partial Enzymatic Activity.,Gay SC, Zhang H, Wilderman PR, Roberts AG, Liu T, Li S, Lin HL, Zhang Q, Woods VL, Stout CD, Hollenberg PF, Halpert JR Biochemistry. 2011 Apr 21. PMID:21510666<ref>PMID:21510666</ref>
+
-
 
+
-
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+
-
</div>
+
==See Also==
==See Also==
-
*[[Cytochrome P450|Cytochrome P450]]
+
*[[Cytochrome P450 3D structures|Cytochrome P450 3D structures]]
-
== References ==
+
-
<references/>
+
__TOC__
__TOC__
</StructureSection>
</StructureSection>
 +
[[Category: Large Structures]]
[[Category: Oryctolagus cuniculus]]
[[Category: Oryctolagus cuniculus]]
-
[[Category: Unspecific monooxygenase]]
+
[[Category: Gay SC]]
-
[[Category: Gay, S C]]
+
[[Category: Halpert JR]]
-
[[Category: Halpert, J R]]
+
[[Category: Hollenberg PF]]
-
[[Category: Hollenberg, P F]]
+
[[Category: Stout CD]]
-
[[Category: Stout, C D]]
+
[[Category: Zhang H]]
-
[[Category: Zhang, H]]
+
-
[[Category: Cytochrome p450 2b4]]
+
-
[[Category: Membrane protein]]
+
-
[[Category: Monooxygenase]]
+
-
[[Category: Oxidoreductase]]
+
-
[[Category: Oxidoreductase-oxidoreductase inhibitor complex]]
+
-
[[Category: T302 covalently linked to tert-butylphenylacetylene]]
+

Current revision

Closed crystal structure of cytochrome P450 2B4 covalently bound to the mechanism-based inactivator tert-butylphenylacetylene

PDB ID 3r1a

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3r1a"
Personal tools