View source for 4iru


==Crystal Structure of lepB GAP core in a transition state mimetic complex with Rab1A and ALF3==
<StructureSection load='4iru' size='340' side='right'caption='[[4iru]], [[Resolution|resolution]] 3.20&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4iru]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Legionella_pneumophila_subsp._pneumophila_str._Philadelphia_1 Legionella pneumophila subsp. pneumophila str. Philadelphia 1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4IRU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4IRU 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]] 3.2&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=AF3:ALUMINUM+FLUORIDE'>AF3</scene>, <scene name='pdbligand=GDP:GUANOSINE-5-DIPHOSPHATE'>GDP</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</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=4iru FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4iru OCA], [https://pdbe.org/4iru PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4iru RCSB], [https://www.ebi.ac.uk/pdbsum/4iru PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4iru ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/Q5ZSM7_LEGPH Q5ZSM7_LEGPH] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
GTPase activating proteins (GAPs) from pathogenic bacteria and eukaryotic host organisms deactivate Rab GTPases by supplying catalytic arginine and glutamine fingers in trans, and utilizing the cis glutamine in the DxxGQ motif of the GTPase for binding rather than catalysis. Here, we report the transition state mimetic structure of the Legionella pneumophila GAP LepB in complex with Rab1 and describe a comprehensive structure-based mutational analysis of potential catalytic and recognition determinants. The results demonstrate that LepB does not simply mimic other GAPs but instead deploys an expected arginine finger in conjunction with a novel glutamic acid finger, which forms a salt bridge with an indispensible switch II arginine that effectively locks the cis glutamine in the DxxGQ motif of Rab1 in a catalytically competent though unprecedented transition state configuration. Surprisingly, a heretofore universal transition state interaction with the cis glutamine is supplanted by an elaborate polar network involving critical P-loop and switch I serines. LepB further employs an unusual tandem domain architecture to clamp a switch I tyrosine in an open conformation that facilitates access of the arginine finger to the hydrolytic site. Intriguingly, the critical P-loop serine corresponds to an oncogenic substitution in Ras and replaces a conserved glycine essential for the canonical transition state stereochemistry. In addition to expanding GTP hydrolytic paradigms, these observations reveal the unconventional dual finger and non-canonical catalytic network mechanisms of Rab GAPs as necessary alternative solutions to a major impediment imposed by substitution of the conserved P-loop glycine.

The Legionella pneumophila GTPase Activating Protein LepB Accelerates Rab1 Deactivation by a Non-Canonical Hydrolytic Mechanism.,Mishra AK, Del Campo CM, Collins RE, Roy CR, Lambright DG J Biol Chem. 2013 Jul 2. PMID:23821544<ref>PMID:23821544</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4iru" style="background-color:#fffaf0;"></div>

==See Also==
*[[Ras-related protein Rab 3D structures|Ras-related protein Rab 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Legionella pneumophila subsp. pneumophila str. Philadelphia 1]]
[[Category: Collins RE]]
[[Category: Delcampo CM]]
[[Category: Lambright DG]]
[[Category: Mishra AK]]
[[Category: Roy CR]]