3dwf

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(Difference between revisions)

Revision as of 16:01, 9 February 2016

Crystal Structure of the Guinea Pig 11beta-Hydroxysteroid Dehydrogenase Type 1 Mutant F278E

Structural highlights

3dwf is a 4 chain structure with sequence from Cavpo. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, ,
Gene:	HSD11B1 (CAVPO)
Activity:	11-beta-hydroxysteroid dehydrogenase, with EC number 1.1.1.146
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum

Function

[DHI1_CAVPO] Catalyzes reversibly the conversion of cortisol to the inactive metabolite cortisone. Catalyzes reversibly the conversion of 7-ketocholesterol to 7-beta-hydroxycholesterol. In intact cells, the reaction runs only in one direction, from 7-ketocholesterol to 7-beta-hydroxycholesterol (By similarity).^[1]

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

11 beta-Hydroxysteroid dehydrogenase type 1 (11 beta-HSD1) is a key enzyme in the conversion of cortisone to the functional glucocorticoid hormone cortisol. This activation has been implicated in several human disorders, notably the metabolic syndrome where 11 beta-HSD1 has been identified as a novel target for potential therapeutic drugs. Recent crystal structures have revealed the presence of a pronounced hydrophobic surface patch lying on two helices at the C-terminus. The physiological significance of this region has been attributed to facilitating substrate access by allowing interactions with the endoplasmic reticulum membrane. Here, we report that single mutations that alter the hydrophobicity of this patch (I275E, L266E, F278E, and L279E in the human enzyme and I275E, Y266E, F278E, and L279E in the guinea pig enzyme) result in greatly increased yields of soluble protein on expression in E. coli. Kinetic analyses of both reductase and dehydrogenase reactions indicate that the F278E mutant has unaltered K(m) values for steroids and an unaltered or increased k(cat). Analytical ultracentrifugation shows that this mutation also decreases aggregation of both the human and guinea pig enzymes, resulting in greater monodispersity. One of the mutants (guinea pig F278E) has proven easy to crystallize and has been shown to have a virtually identical structure to that previously reported for the wild-type enzyme. The human F278E enzyme is shown to be a suitable background for analyzing the effects of naturally occurring mutations (R137C, K187N) on enzyme activity and stability. Hence, the F278E mutants should be useful for many future biochemical and biophysical studies of the enzyme.

Mutations of key hydrophobic surface residues of 11 beta-hydroxysteroid dehydrogenase type 1 increase solubility and monodispersity in a bacterial expression system.,Lawson AJ, Walker EA, White SA, Dafforn TR, Stewart PM, Ride JP Protein Sci. 2009 Jul;18(7):1552-63. PMID:19507261^[2]

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

References

↑ Pu X, Yang K. Guinea pig 11beta-hydroxysteroid dehydrogenase type 1: primary structure and catalytic properties. Steroids. 2000 Mar;65(3):148-56. PMID:10699594
↑ Lawson AJ, Walker EA, White SA, Dafforn TR, Stewart PM, Ride JP. Mutations of key hydrophobic surface residues of 11 beta-hydroxysteroid dehydrogenase type 1 increase solubility and monodispersity in a bacterial expression system. Protein Sci. 2009 Jul;18(7):1552-63. PMID:19507261 doi:10.1002/pro.150

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3dwf"

@@ Line 2: / Line 2: @@
 <StructureSection load='3dwf' size='340' side='right' caption='[[3dwf]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[3dwf]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Cavia_porcellus Cavia porcellus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3DWF OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3DWF FirstGlance]. <br>
+<table><tr><td colspan='2'>[[3dwf]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Cavpo Cavpo]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3DWF OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3DWF FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">HSD11B1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10141 Cavia porcellus])</td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">HSD11B1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10141 CAVPO])</td></tr>
 <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/11-beta-hydroxysteroid_dehydrogenase 11-beta-hydroxysteroid dehydrogenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.1.1.146 1.1.1.146] </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=3dwf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3dwf OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3dwf RCSB], [http://www.ebi.ac.uk/pdbsum/3dwf PDBsum]</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=3dwf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3dwf OCA], [http://pdbe.org/3dwf PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3dwf RCSB], [http://www.ebi.ac.uk/pdbsum/3dwf PDBsum]</span></td></tr>
 </table>
 == Function ==
@@ Line 18: / Line 18: @@
     <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/chain_selection.php?pdb_ID=2ata ConSurf].
+</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=3dwf ConSurf].
 <div style="clear:both"></div>
 <div style="background-color:#fffaf0;">
@@ Line 28: / Line 28: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 3dwf" style="background-color:#fffaf0;"></div>
 ==See Also==
@@ Line 36: / Line 37: @@
 </StructureSection>
 [[Category: 11-beta-hydroxysteroid dehydrogenase]]
-[[Category: Cavia porcellus]]
+[[Category: Cavpo]]
 [[Category: Lawson, A J]]
 [[Category: Ride, J P]]

3dwf

From Proteopedia

Revision as of 16:01, 9 February 2016

Crystal Structure of the Guinea Pig 11beta-Hydroxysteroid Dehydrogenase Type 1 Mutant F278E

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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