2wud

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Revision as of 20:52, 4 August 2016

CRYSTAL STRUCTURE OF S114A MUTANT OF HSAD FROM MYCOBACTERIUM TUBERCULOSIS

Structural highlights

2wud is a 2 chain structure with sequence from Myctu. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Related:	2vf2, 2wue, 2wuf, 2wug
Activity:	2,6-dioxo-6-phenylhexa-3-enoate hydrolase, with EC number 3.7.1.8
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[HSAD_MYCTO] Catalyzes the hydrolysis of a carbon-carbon bond in 4,5: 9,10-diseco-3-hydroxy-5,9,17-trioxoandrosta-1(10),2-diene-4-oate (4,9-DSHA) to yield 9,17-dioxo-1,2,3,4,10,19-hexanorandrostan-5-oate (DOHNAA) and 2-hydroxy-hexa-2,4-dienoate (HHD). Is also able to catalyze the hydrolysis of 2-hydroxy-6-oxo-6-phenylhexa-2,4-dienoic acid (HOPDA) and the synthetic analog 8-(2-chlorophenyl)-2-hydroxy-5-methyl-6-oxoocta-2,4-dienoic acid (HOPODA) (By similarity).

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

In the recently identified cholesterol catabolic pathway of Mycobacterium tuberculosis, 2-hydroxy-6-oxo-6-phenylhexa-2,4-dienoate hydrolase (HsaD) is proposed to catalyze the hydrolysis of a carbon-carbon bond in 4,5-9,10-diseco-3-hydroxy-5,9,17-tri-oxoandrosta-1(10),2-diene-4-oic acid (DSHA), the cholesterol meta-cleavage product (MCP) and has been implicated in the intracellular survival of the pathogen. Herein, purified HsaD demonstrated 4-33 times higher specificity for DSHA (k(cat)/K(m) = 3.3 +/- 0.3 x 10(4) m(-1) s(-1)) than for the biphenyl MCP 2-hydroxy-6-oxo-6-phenylhexa-2,4-dienoic acid (HOPDA) and the synthetic analogue 8-(2-chlorophenyl)-2-hydroxy-5-methyl-6-oxoocta-2,4-dienoic acid (HOPODA), respectively. The S114A variant of HsaD, in which the active site serine was substituted with alanine, was catalytically impaired and bound DSHA with a K(d) of 51 +/- 2 mum. The S114A.DSHA species absorbed maximally at 456 nm, 60 nm red-shifted versus the DSHA enolate. Crystal structures of the variant in complex with HOPDA, HOPODA, or DSHA to 1.8-1.9 Aindicate that this shift is due to the enzyme-induced strain of the enolate. These data indicate that the catalytic serine catalyzes tautomerization. A second role for this residue is suggested by a solvent molecule whose position in all structures is consistent with its activation by the serine for the nucleophilic attack of the substrate. Finally, the alpha-helical lid covering the active site displayed a ligand-dependent conformational change involving differences in side chain carbon positions of up to 6.7 A, supporting a two-conformation enzymatic mechanism. Overall, these results provide novel insights into the determinants of specificity in a mycobacterial cholesterol-degrading enzyme as well as into the mechanism of MCP hydrolases.

Characterization of a carbon-carbon hydrolase from Mycobacterium tuberculosis involved in cholesterol metabolism.,Lack NA, Yam KC, Lowe ED, Horsman GP, Owen RL, Sim E, Eltis LD J Biol Chem. 2010 Jan 1;285(1):434-43. Epub 2009 Oct 29. PMID:19875455^[1]

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

References

↑ Lack NA, Yam KC, Lowe ED, Horsman GP, Owen RL, Sim E, Eltis LD. Characterization of a carbon-carbon hydrolase from Mycobacterium tuberculosis involved in cholesterol metabolism. J Biol Chem. 2010 Jan 1;285(1):434-43. Epub 2009 Oct 29. PMID:19875455 doi:10.1074/jbc.M109.058081

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/2wud"

@@ Line 1: / Line 1: @@
 ==CRYSTAL STRUCTURE OF S114A MUTANT OF HSAD FROM MYCOBACTERIUM TUBERCULOSIS==
 <StructureSection load='2wud' size='340' side='right' caption='[[2wud]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[2wud]] 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=2WUD OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2WUD FirstGlance]. <br>
+<table><tr><td colspan='2'>[[2wud]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Myctu Myctu]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2WUD OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2WUD FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=SCN:THIOCYANATE+ION'>SCN</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2vf2|2vf2]], [[2wue|2wue]], [[2wuf|2wuf]], [[2wug|2wug]]</td></tr>
 <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/2,6-dioxo-6-phenylhexa-3-enoate_hydrolase 2,6-dioxo-6-phenylhexa-3-enoate hydrolase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.7.1.8 3.7.1.8] </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=2wud FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2wud OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2wud RCSB], [http://www.ebi.ac.uk/pdbsum/2wud 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=2wud FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2wud OCA], [http://pdbe.org/2wud PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2wud RCSB], [http://www.ebi.ac.uk/pdbsum/2wud PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2wud ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[http://www.uniprot.org/uniprot/P96851_MYCTU P96851_MYCTU]] Catalyzes the hydrolysis of a carbon-carbon bond in 4,5: 9,10-diseco-3-hydroxy-5,9,17-trioxoandrosta-1(10),2-diene-4-oate (4,9-DSHA) to yield 9,17-dioxo-1,2,3,4,10,19-hexanorandrostan-5-oate (DOHNAA) and 2-hydroxy-hexa-2,4-dienoate (HHD). Is also able to catalyze the hydrolysis of 2-hydroxy-6-oxo-6-phenylhexa-2,4-dienoic acid (HOPDA) and the synthetic analog 8-(2-chlorophenyl)-2-hydroxy-5-methyl-6-oxoocta-2,4-dienoic acid (HOPODA) (By similarity).
+[[http://www.uniprot.org/uniprot/HSAD_MYCTO HSAD_MYCTO]] Catalyzes the hydrolysis of a carbon-carbon bond in 4,5: 9,10-diseco-3-hydroxy-5,9,17-trioxoandrosta-1(10),2-diene-4-oate (4,9-DSHA) to yield 9,17-dioxo-1,2,3,4,10,19-hexanorandrostan-5-oate (DOHNAA) and 2-hydroxy-hexa-2,4-dienoate (HHD). Is also able to catalyze the hydrolysis of 2-hydroxy-6-oxo-6-phenylhexa-2,4-dienoic acid (HOPDA) and the synthetic analog 8-(2-chlorophenyl)-2-hydroxy-5-methyl-6-oxoocta-2,4-dienoic acid (HOPODA) (By similarity).
 == Evolutionary Conservation ==
 [[Image:Consurf_key_small.gif|200px|right]]
@@ Line 18: / Line 19: @@
     <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=2wud ConSurf].
 <div style="clear:both"></div>
 <div style="background-color:#fffaf0;">
@@ Line 28: / Line 29: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 2wud" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>
@@ Line 33: / Line 35: @@
 </StructureSection>
 [[Category: 2,6-dioxo-6-phenylhexa-3-enoate hydrolase]]
-[[Category: Mycobacterium tuberculosis]]
+[[Category: Myctu]]
 [[Category: Eltis, L D]]
 [[Category: Horsman, G P]]

2wud

From Proteopedia

Revision as of 20:52, 4 August 2016

CRYSTAL STRUCTURE OF S114A MUTANT OF HSAD FROM MYCOBACTERIUM TUBERCULOSIS

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

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