1sqm

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
(New page: 200px<br /> <applet load="1sqm" size="450" color="white" frame="true" align="right" spinBox="true" caption="1sqm, resolution 2.30&Aring;" /> '''STRUCTURE OF [R563A...)
Current revision (08:33, 14 February 2024) (edit) (undo)
 
(16 intermediate revisions not shown.)
Line 1: Line 1:
-
[[Image:1sqm.gif|left|200px]]<br />
 
-
<applet load="1sqm" size="450" color="white" frame="true" align="right" spinBox="true"
 
-
caption="1sqm, resolution 2.30&Aring;" />
 
-
'''STRUCTURE OF [R563A] LEUKOTRIENE A4 HYDROLASE'''<br />
 
-
==Overview==
+
==STRUCTURE OF [R563A] LEUKOTRIENE A4 HYDROLASE==
-
Leukotriene (LT) A(4) hydrolase is a bifunctional zinc metalloenzyme, which converts LTA(4) into the neutrophil chemoattractant LTB(4) and also, exhibits an anion-dependent aminopeptidase activity. In the x-ray crystal, structure of LTA(4) hydrolase, Arg(563) and Lys(565) are found at the, entrance of the active center. Here we report that replacement of, Arg(563), but not Lys(565), leads to complete abrogation of the epoxide, hydrolase activity. However, mutations of Arg(563) do not seem to affect, substrate binding strength, because values of K(i) for LTA(4) are almost, identical for wild type and (R563K)LTA(4) hydrolase. These results are, supported by the 2.3-A crystal structure of (R563A)LTA(4) hydrolase, which, does not reveal structural changes that can explain the complete loss of, enzyme function. For the aminopeptidase reaction, mutations of Arg(563), reduce the catalytic activity (V(max) = 0.3-20%), whereas mutations of, Lys(565) have limited effect on catalysis (V(max) = 58-108%). However, in, (K565A)- and (K565M)LTA(4) hydrolase, i.e. mutants lacking a positive, charge, values of the Michaelis constant for alanine-p-nitroanilide, increase significantly (K(m) = 480-640%). Together, our data indicate that, Arg(563) plays an unexpected, critical role in the epoxide hydrolase, reaction, presumably in the positioning of the carboxylate tail to ensure, perfect substrate alignment along the catalytic elements of the active, site. In the aminopeptidase reaction, Arg(563) and Lys(565) seem to, cooperate to provide sufficient binding strength and productive alignment, of the substrate. In conclusion, Arg(563) and Lys(565) possess distinct, roles as carboxylate recognition sites for two chemically different, substrates, each of which is turned over in separate enzymatic reactions, catalyzed by LTA(4) hydrolase.
+
<StructureSection load='1sqm' size='340' side='right'caption='[[1sqm]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
 +
== Structural highlights ==
 +
<table><tr><td colspan='2'>[[1sqm]] 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=1SQM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1SQM 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]] 2.3&#8491;</td></tr>
 +
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACY:ACETIC+ACID'>ACY</scene>, <scene name='pdbligand=IMD:IMIDAZOLE'>IMD</scene>, <scene name='pdbligand=YB:YTTERBIUM+(III)+ION'>YB</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=1sqm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1sqm OCA], [https://pdbe.org/1sqm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1sqm RCSB], [https://www.ebi.ac.uk/pdbsum/1sqm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1sqm ProSAT]</span></td></tr>
 +
</table>
 +
== Function ==
 +
[https://www.uniprot.org/uniprot/LKHA4_HUMAN LKHA4_HUMAN] Epoxide hydrolase that catalyzes the final step in the biosynthesis of the proinflammatory mediator leukotriene B4. Has also aminopeptidase activity.<ref>PMID:1897988</ref> <ref>PMID:1975494</ref> <ref>PMID:2244921</ref> <ref>PMID:12207002</ref> <ref>PMID:11917124</ref> <ref>PMID:15078870</ref> <ref>PMID:18804029</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/sq/1sqm_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=1sqm ConSurf].
 +
<div style="clear:both"></div>
-
==About this Structure==
+
==See Also==
-
1SQM 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 ZN, YB, IMD and ACY as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Leukotriene-A(4)_hydrolase Leukotriene-A(4) hydrolase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.3.2.6 3.3.2.6] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1SQM OCA].
+
*[[Leukotriene A4 Hydrolase|Leukotriene A4 Hydrolase]]
-
 
+
== References ==
-
==Reference==
+
<references/>
-
Leukotriene A4 hydrolase: identification of a common carboxylate recognition site for the epoxide hydrolase and aminopeptidase substrates., Rudberg PC, Tholander F, Andberg M, Thunnissen MM, Haeggstrom JZ, J Biol Chem. 2004 Jun 25;279(26):27376-82. Epub 2004 Apr 12. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=15078870 15078870]
+
__TOC__
 +
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
-
[[Category: Leukotriene-A(4) hydrolase]]
+
[[Category: Large Structures]]
-
[[Category: Single protein]]
+
[[Category: Haeggstrom JZ]]
-
[[Category: Haeggstrom, J.Z.]]
+
[[Category: Rudberg PC]]
-
[[Category: Rudberg, P.C.]]
+
[[Category: Tholander FOT]]
-
[[Category: Tholander, F.O.T.]]
+
[[Category: Thunnissen MMGM]]
-
[[Category: Thunnissen, M.M.G.M.]]
+
-
[[Category: ACY]]
+
-
[[Category: IMD]]
+
-
[[Category: YB]]
+
-
[[Category: ZN]]
+
-
[[Category: epoxide hydrolase; alpha-beta protein; leukotriene biosynthesis; metalloprotease]]
+
-
 
+
-
''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 19:16:51 2007''
+

Current revision

STRUCTURE OF [R563A] LEUKOTRIENE A4 HYDROLASE

PDB ID 1sqm

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/1sqm"
Personal tools