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1n28

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(New page: 200px<br /> <applet load="1n28" size="450" color="white" frame="true" align="right" spinBox="true" caption="1n28, resolution 1.5&Aring;" /> '''Crystal structure of...)
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[[Image:1n28.gif|left|200px]]<br />
 
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<applet load="1n28" size="450" color="white" frame="true" align="right" spinBox="true"
 
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caption="1n28, resolution 1.5&Aring;" />
 
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'''Crystal structure of the H48Q mutant of human group IIA phospholipase A2'''<br />
 
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==Overview==
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==Crystal structure of the H48Q mutant of human group IIA phospholipase A2==
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The human group IIA secreted PLA(2) is a 14 kDa calcium-dependent, extracellular enzyme that has been characterized as an acute phase protein, with important antimicrobial activity and has been implicated in signal, transduction. The selective binding of this enzyme to the phospholipid, substrate interface plays a crucial role in its physiological function. To, study interfacial binding in the absence of catalysis, one strategy is to, produce structurally intact but catalytically inactive mutants. The active, site mutants H48Q, H48N, and H48A had been prepared for the secreted, PLA(2)s from bovine pancreas and bee venom and retained minimal catalytic, activity while the H48Q mutant showed the maximum structural integrity., Preparation of the mutant H48Q of the human group IIA enzyme unexpectedly, produced an enzyme that retained significant (2-4%) catalytic activity, that was contrary to expectations in view of the accepted catalytic, mechanism. In this paper it is established that the high residual activity, of the H48Q mutant is genuine, not due to contamination, and can be seen, under a variety of assay conditions including assays in the presence of, Co(2+) and Ni(2+) in place of Ca(2+). The crystallization of the H48Q, mutant, yielding diffraction data to a resolution of 1.5 A, allowed a, comparison with the corresponding recombinant wild-type enzyme (N1A) that, was also crystallized. This comparison revealed that all of the important, features of the catalytic machinery were in place and the two structures, were virtually superimposable. In particular, the catalytic calcium ion, occupied an identical position in the active site of the two proteins, and, the catalytic water molecule (w6) was clearly resolved in the H48Q mutant., We propose that a variation of the calcium-coordinated oxyanion ("two, water") mechanism involving hydrogen bonding rather than the anticipated, full proton transfer to the histidine will best explain the ability of an, active site glutamine to allow significant catalytic activity.
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<StructureSection load='1n28' size='340' side='right'caption='[[1n28]], [[Resolution|resolution]] 1.50&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[1n28]] is a 2 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=1N28 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1N28 FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.5&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1n28 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1n28 OCA], [https://pdbe.org/1n28 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1n28 RCSB], [https://www.ebi.ac.uk/pdbsum/1n28 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1n28 ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/PA2GA_HUMAN PA2GA_HUMAN] Thought to participate in the regulation of the phospholipid metabolism in biomembranes including eicosanoid biosynthesis. Catalyzes the calcium-dependent hydrolysis of the 2-acyl groups in 3-sn-phosphoglycerides.
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/n2/1n28_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</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=1n28 ConSurf].
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<div style="clear:both"></div>
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==Disease==
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==See Also==
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Known diseases associated with this structure: Colorectal cancer, sporadic OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=172411 172411]]
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*[[Phospholipase A2 3D structures|Phospholipase A2 3D structures]]
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__TOC__
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==About this Structure==
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</StructureSection>
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1N28 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 CA as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Phospholipase_A(2) Phospholipase A(2)], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.1.4 3.1.1.4] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1N28 OCA].
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==Reference==
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The crystal structure of the H48Q active site mutant of human group IIA secreted phospholipase A2 at 1.5 A resolution provides an insight into the catalytic mechanism., Edwards SH, Thompson D, Baker SF, Wood SP, Wilton DC, Biochemistry. 2002 Dec 31;41(52):15468-76. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=12501175 12501175]
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[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Phospholipase A(2)]]
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[[Category: Large Structures]]
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[[Category: Single protein]]
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[[Category: Baker SF]]
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[[Category: Baker, S.F.]]
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[[Category: Edwards SH]]
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[[Category: Edwards, S.H.]]
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[[Category: Thompson D]]
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[[Category: Thompson, D.]]
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[[Category: Wilton DC]]
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[[Category: Wilton, D.C.]]
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[[Category: Wood SP]]
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[[Category: Wood, S.P.]]
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[[Category: CA]]
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[[Category: hydrolase]]
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''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 18:17:00 2007''
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Current revision

Crystal structure of the H48Q mutant of human group IIA phospholipase A2

PDB ID 1n28

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