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3aff

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Crystal structure of the HsaA monooxygenase from M. tuberculosis

Structural highlights

3aff is a 2 chain structure with sequence from Mycobacterium tuberculosis. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2Å
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

HSAA_MYCTU Catalyzes the o-hydroxylation of 3-hydroxy-9,10-secoandrosta-1,3,5(10)-triene-9,17-dione (3-HSA) to 3,4-dihydroxy-9,10-secoandrosta-1,3,5(10)-triene-9,17-dione (3,4-DHSA) in the catabolism of cholesterol. Can use either FADH(2) or FMNH(2) as flavin cosubstrate. Also catalyzes the o-hydroxylation of a range of p-substituted phenols to generate the corresponding catechols.^[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

Mycobacterium tuberculosis (Mtb) and Rhodococcus jostii RHA1 have similar cholesterol catabolic pathways. This pathway contributes to the pathogenicity of Mtb. The hsaAB cholesterol catabolic genes have been predicted to encode the oxygenase and reductase, respectively, of a flavin-dependent mono-oxygenase that hydroxylates 3-hydroxy-9,10-seconandrost-1,3,5(10)-triene-9,17-dione (3-HSA) to a catechol. An hsaA deletion mutant of RHA1 did not grow on cholesterol but transformed the latter to 3-HSA and related metabolites in which each of the two keto groups was reduced: 3,9-dihydroxy-9,10-seconandrost-1,3,5(10)-triene-17-one (3,9-DHSA) and 3,17-dihydroxy-9,10-seconandrost-1,3,5(10)-triene-9-one (3,17-DHSA). Purified 3-hydroxy-9,10-seconandrost-1,3,5(10)-triene-9,17-dione 4-hydroxylase (HsaAB) from Mtb had higher specificity for 3-HSA than for 3,17-DHSA (apparent k(cat)/K(m) = 1000 +/- 100 M(-1) s(-1) versus 700 +/- 100 M(-1) s(-1)). However, 3,9-DHSA was a poorer substrate than 3-hydroxybiphenyl (apparent k(cat)/K(m) = 80 +/- 40 M(-1) s(-1)). In the presence of 3-HSA the K(m)(app) for O(2) was 100 +/- 10 microM. The crystal structure of HsaA to 2.5-A resolution revealed that the enzyme has the same fold, flavin-binding site, and catalytic residues as p-hydroxyphenyl acetate hydroxylase. However, HsaA has a much larger phenol-binding site, consistent with the enzyme's substrate specificity. In addition, a second crystal form of HsaA revealed that a C-terminal flap (Val(367)-Val(394)) could adopt two conformations differing by a rigid body rotation of 25 degrees around Arg(366). This rotation appears to gate the likely flavin entrance to the active site. In docking studies with 3-HSA and flavin, the closed conformation provided a rationale for the enzyme's substrate specificity. Overall, the structural and functional data establish the physiological role of HsaAB and provide a basis to further investigate an important class of monooxygenases as well as the bacterial catabolism of steroids.

A flavin-dependent monooxygenase from Mycobacterium tuberculosis involved in cholesterol catabolism.,Dresen C, Lin LY, D'Angelo I, Tocheva EI, Strynadka N, Eltis LD J Biol Chem. 2010 Jul 16;285(29):22264-75. Epub 2010 May 6. PMID:20448045^[2]

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

References

↑ Dresen C, Lin LY, D'Angelo I, Tocheva EI, Strynadka N, Eltis LD. A flavin-dependent monooxygenase from Mycobacterium tuberculosis involved in cholesterol catabolism. J Biol Chem. 2010 Jul 16;285(29):22264-75. Epub 2010 May 6. PMID:20448045 doi:10.1074/jbc.M109.099028
↑ Dresen C, Lin LY, D'Angelo I, Tocheva EI, Strynadka N, Eltis LD. A flavin-dependent monooxygenase from Mycobacterium tuberculosis involved in cholesterol catabolism. J Biol Chem. 2010 Jul 16;285(29):22264-75. Epub 2010 May 6. PMID:20448045 doi:10.1074/jbc.M109.099028

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

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

@@ Line 1: / Line 1: @@
 ==Crystal structure of the HsaA monooxygenase from M. tuberculosis==
-<StructureSection load='3aff' size='340' side='right' caption='[[3aff]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
+<StructureSection load='3aff' size='340' side='right'caption='[[3aff]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[3aff]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Mycobacterium_tuberculosis Mycobacterium tuberculosis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3AFF OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3AFF FirstGlance]. <br>
+<table><tr><td colspan='2'>[[3aff]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycobacterium_tuberculosis Mycobacterium tuberculosis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3AFF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3AFF FirstGlance]. <br>
-</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3afe|3afe]]</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]] 2&#8491;</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=3aff FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3aff OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3aff RCSB], [http://www.ebi.ac.uk/pdbsum/3aff PDBsum]</span></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=3aff FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3aff OCA], [https://pdbe.org/3aff PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3aff RCSB], [https://www.ebi.ac.uk/pdbsum/3aff PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3aff ProSAT]</span></td></tr>
 </table>
+== Function ==
+[https://www.uniprot.org/uniprot/HSAA_MYCTU HSAA_MYCTU] Catalyzes the o-hydroxylation of 3-hydroxy-9,10-secoandrosta-1,3,5(10)-triene-9,17-dione (3-HSA) to 3,4-dihydroxy-9,10-secoandrosta-1,3,5(10)-triene-9,17-dione (3,4-DHSA) in the catabolism of cholesterol. Can use either FADH(2) or FMNH(2) as flavin cosubstrate. Also catalyzes the o-hydroxylation of a range of p-substituted phenols to generate the corresponding catechols.<ref>PMID:20448045</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/af/3aff_consurf.spt"</scriptWhenChecked>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/af/3aff_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/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=3aff ConSurf].
 <div style="clear:both"></div>
 <div style="background-color:#fffaf0;">
@@ Line 24: / Line 27: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 3aff" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>
 __TOC__
 </StructureSection>
+[[Category: Large Structures]]
 [[Category: Mycobacterium tuberculosis]]
-[[Category: Angelo, I D]]
+[[Category: D'Angelo I]]
-[[Category: Dresen, C]]
+[[Category: Dresen C]]
-[[Category: Eltis, L D]]
+[[Category: Eltis LD]]
-[[Category: Lin, L Y]]
+[[Category: Lin LY]]
-[[Category: Strynadka, N]]
+[[Category: Strynadka N]]
-[[Category: Tocheva, E I]]
+[[Category: Tocheva EI]]
-[[Category: Cholesterol 3hsa monooxygenase]]
-[[Category: Hsaa]]
-[[Category: Oxidoreductase]]

3aff

From Proteopedia

Current revision

Crystal structure of the HsaA monooxygenase from M. tuberculosis

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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