4j3b
From Proteopedia
(Difference between revisions)
| Line 1: | Line 1: | ||
| - | + | ==A naturally variable residue in the S1 subsite of M1-family aminopeptidases modulates catalytic properties and promotes functional specialization== | |
| - | + | <StructureSection load='4j3b' size='340' side='right' caption='[[4j3b]], [[Resolution|resolution]] 2.20Å' scene=''> | |
| - | + | == Structural highlights == | |
| + | <table><tr><td colspan='2'>[[4j3b]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Plasmodium_falciparum_fcb1/columbia Plasmodium falciparum fcb1/columbia]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4J3B OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4J3B FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ARG:ARGININE'>ARG</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | ||
| + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">P.falciparum ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=186763 Plasmodium falciparum FcB1/Columbia])</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=4j3b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4j3b OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4j3b RCSB], [http://www.ebi.ac.uk/pdbsum/4j3b PDBsum]</span></td></tr> | ||
| + | </table> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | M1-family metallo-aminopeptidases fulfill a wide range of critical and in some cases medically relevant roles in humans and human pathogens. The specificity of M1-aminopeptidases is dominated by the interaction of the well-defined S1 subsite with the sidechain of the first (P1) residue of the substrate and can vary widely. Extensive natural variation occurs at one of the residues that contributes to formation of the cylindrical S1 subsite. We investigated whether this natural variation contributes to diversity in S1 subsite specificity. Effects of eleven substitutions of the S1 subsite residue valine 459 in the Plasmodium falciparum aminopeptidase PfA-M1 and of three substitutions of the homologous residue methionine 260 in Escherichia coli PepN were characterized. Many of these substitutions altered steady-state kinetic parameters for dipeptide hydrolysis and remodeled S1 subsite specificity. The most dramatic change in specificity resulted from substitution with proline, which collapsed S1 subsite specificity such that only substrates with P1-Arg, -Lys or -Met were appreciably hydrolyzed. The structure of PfA-M1 V459P revealed that the proline substitution induced a local conformational change in the polypeptide backbone that resulted in a narrowed S1 subsite. The restricted specificity and active site backbone conformation of PfA-M1 V459P mirrored those of endoplasmic reticulum aminopeptidase 2, a human enzyme with proline in the variable S1 subsite position. Our results provide compelling evidence that changes in the variable residue in the S1 subsite of M1-aminopeptidases have facilitated the evolution of new specificities and ultimately novel functions for this important class of enzymes. | ||
| - | + | A naturally variable residue in the S1 subsite of M1-family aminopeptidases modulates catalytic properties and promotes functional specialization.,Dalal S, Ragheb DR, Schubot FD, Klemba M J Biol Chem. 2013 Jul 29. PMID:23897806<ref>PMID:23897806</ref> | |
| - | + | ||
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | + | </div> | |
==See Also== | ==See Also== | ||
*[[Aminopeptidase|Aminopeptidase]] | *[[Aminopeptidase|Aminopeptidase]] | ||
| - | + | == References == | |
| - | == | + | <references/> |
| - | + | __TOC__ | |
| + | </StructureSection> | ||
[[Category: Plasmodium falciparum fcb1/columbia]] | [[Category: Plasmodium falciparum fcb1/columbia]] | ||
| - | [[Category: Dalal, S | + | [[Category: Dalal, S]] |
| - | [[Category: Klemba, M | + | [[Category: Klemba, M]] |
| - | [[Category: Ragheb, D R.T | + | [[Category: Ragheb, D R.T]] |
| - | [[Category: Schubot, F D | + | [[Category: Schubot, F D]] |
[[Category: Hydrolase]] | [[Category: Hydrolase]] | ||
[[Category: Peptide]] | [[Category: Peptide]] | ||
[[Category: Protease]] | [[Category: Protease]] | ||
Revision as of 12:18, 21 December 2014
A naturally variable residue in the S1 subsite of M1-family aminopeptidases modulates catalytic properties and promotes functional specialization
| |||||||||||
