View source for 3gmw


==Crystal Structure of Beta-Lactamse Inhibitory Protein-I (BLIP-I) in Complex with TEM-1 Beta-Lactamase==
<StructureSection load='3gmw' size='340' side='right'caption='[[3gmw]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[3gmw]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/"actinomyces_exfoliatus"_waksman_and_curtis_1916 "actinomyces exfoliatus" waksman and curtis 1916] and [https://en.wikipedia.org/wiki/Escherichia_sp._sflu5 Escherichia sp. sflu5]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3GMW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3GMW FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3gmu|3gmu]], [[3gmv|3gmv]], [[3gmx|3gmx]], [[3gmy|3gmy]]</div></td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">amp, bla ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=299586 Escherichia sp. Sflu5]), bliA ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1905 "Actinomyces exfoliatus" Waksman and Curtis 1916])</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=3gmw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3gmw OCA], [https://pdbe.org/3gmw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3gmw RCSB], [https://www.ebi.ac.uk/pdbsum/3gmw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3gmw ProSAT]</span></td></tr>
</table>
== 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/gm/3gmw_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=3gmw ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Beta-lactamase inhibitory protein (BLIP) binds a variety of beta-lactamase enzymes with wide-ranging specificity. Its binding mechanism and interface interactions are a well-established model system for the characterization of protein-protein interactions. Published studies have examined the binding of BLIP to diverse target beta-lactamases (e.g., TEM-1, SME-1, and SHV-1). However, apart from point mutations of amino acid residues, variability on the inhibitor side of this enzyme-inhibitor interface has remained unexplored. Thus, we present crystal structures of two likely BLIP relatives: (1) BLIP-I (solved alone and in complex with TEM-1), which has beta-lactamase inhibitory activity very similar to that of BLIP; and (2) beta-lactamase-inhibitory-protein-like protein (BLP) (in two apo forms, including an ultra-high-resolution structure), which is unable to inhibit any tested beta-lactamase. Despite categorical differences in species of origin and function, BLIP-I and BLP share nearly identical backbone conformations, even at loop regions differing in BLIP. We describe interacting residues and provide a comparative structural analysis of the interactions formed at the interface of BLIP-I.TEM-1 versus those formed at the interface of BLIP.TEM-1. Along with initial attempts to functionally characterize BLP, we examine its amino acid residues that structurally correspond to BLIP/BLIP-I binding hotspots to explain its inability to bind and inhibit TEM-1. We conclude that the BLIP family fold is a robust and flexible scaffold that permits the formation of high-affinity protein-protein interactions while remaining highly selective. Comparison of the two naturally occurring, distinct binding interfaces built upon this scaffold (BLIP and BLIP-I) shows that there is substantial variation possible in the subnanomolar binding interaction with TEM-1. The corresponding (non-TEM-1-binding) BLP surface shows that numerous favorable backbone-backbone/backbone-side-chain interactions with a protein partner can be negated by the presence of a few, strongly unfavorable interactions, especially electrostatic repulsions.

Insights into positive and negative requirements for protein-protein interactions by crystallographic analysis of the beta-lactamase inhibitory proteins BLIP, BLIP-I, and BLP.,Gretes M, Lim DC, de Castro L, Jensen SE, Kang SG, Lee KJ, Strynadka NC J Mol Biol. 2009 Jun 5;389(2):289-305. Epub 2009 Mar 28. PMID:19332077<ref>PMID:19332077</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 3gmw" style="background-color:#fffaf0;"></div>

==See Also==
*[[Beta-lactamase 3D structures|Beta-lactamase 3D structures]]
*[[TEM1-beta-Lactamase/beta-lactamase Inhibitor Protein (BLIP)|TEM1-beta-Lactamase/beta-lactamase Inhibitor Protein (BLIP)]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Actinomyces exfoliatus waksman and curtis 1916]]
[[Category: Escherichia sp. sflu5]]
[[Category: Large Structures]]
[[Category: Gretes, M]]
[[Category: Lim, D C]]
[[Category: Strynadka, N C.J]]
[[Category: Antibiotic resistance]]
[[Category: Hydrolase]]
[[Category: Plasmid]]
[[Category: Protein binding]]
[[Category: Protein-protein complex]]