View source for 2p49


==Complex of a camelid single-domain vhh antibody fragment with RNASE A at 1.4A resolution: native mono_1 crystal form==
<StructureSection load='2p49' size='340' side='right' caption='[[2p49]], [[Resolution|resolution]] 1.38&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2p49]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Arabian_camel Arabian camel] and [http://en.wikipedia.org/wiki/Bos_taurus Bos taurus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2P49 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2P49 FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr>
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Pancreatic_ribonuclease Pancreatic ribonuclease], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.27.5 3.1.27.5] </span></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=2p49 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2p49 OCA], [http://pdbe.org/2p49 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2p49 RCSB], [http://www.ebi.ac.uk/pdbsum/2p49 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2p49 ProSAT]</span></td></tr>
</table>
== Function ==
[[http://www.uniprot.org/uniprot/RNAS1_BOVIN RNAS1_BOVIN]] Endonuclease that catalyzes the cleavage of RNA on the 3' side of pyrimidine nucleotides. Acts on single stranded and double stranded RNA.<ref>PMID:7479688</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/p4/2p49_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=2p49 ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
A major architectural class in engineered binding proteins ("antibody mimics") involves the presentation of recognition loops off a single-domain scaffold. This class of binding proteins, both natural and synthetic, has a strong tendency to bind a preformed cleft using a convex binding interface (paratope). To explore their capacity to produce high-affinity interfaces with diverse shape and topography, we examined the interface energetics and explored the affinity limit achievable with a flat paratope. We chose a minimalist paratope limited to two loops found in a natural camelid heavy-chain antibody (VHH) that binds to ribonuclease A. Ala scanning of the VHH revealed only three "hot spot" side chains and additional four residues important for supporting backbone-mediated interactions. The small number of critical residues suggested that this is not an optimized paratope. Using selection from synthetic combinatorial libraries, we enhanced its affinity by &gt;100-fold, resulting in variants with Kd as low as 180 pM with no detectable loss of binding specificity. High-resolution crystal structures revealed that the mutations induced only subtle structural changes but extended the network of interactions. This resulted in an expanded hot spot region including four additional residues located at the periphery of the paratope with a concomitant loss of the so-called "O-ring" arrangement of energetically inert residues. These results suggest that this class of simple, single-domain scaffolds is capable of generating high-performance binding interfaces with diverse shape. More generally, they suggest that highly functional interfaces can be designed without closely mimicking natural interfaces.

Exploring the capacity of minimalist protein interfaces: interface energetics and affinity maturation to picomolar KD of a single-domain antibody with a flat paratope.,Koide A, Tereshko V, Uysal S, Margalef K, Kossiakoff AA, Koide S J Mol Biol. 2007 Nov 2;373(4):941-53. Epub 2007 Aug 21. PMID:17888451<ref>PMID:17888451</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 2p49" style="background-color:#fffaf0;"></div>

==See Also==
*[[Antibody 3D structures|Antibody 3D structures]]
*[[Ribonuclease|Ribonuclease]]
*[[Temp|Temp]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Arabian camel]]
[[Category: Bos taurus]]
[[Category: Pancreatic ribonuclease]]
[[Category: Koide, A]]
[[Category: Koide, S]]
[[Category: Kossiakoff, A A]]
[[Category: Margalef, K]]
[[Category: Tereshko, V]]
[[Category: Uysal, S]]
[[Category: Cab-rn05]]
[[Category: Camelid single-domain antibody]]
[[Category: Hydrolase-immune system complex]]
[[Category: Paratope]]
[[Category: Rnase some]]
[[Category: Vhh]]
[[Category: Yeast surface display]]