1kxv: Difference between revisions
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< | ==Camelid VHH Domains in Complex with Porcine Pancreatic alpha-Amylase== | ||
<StructureSection load='1kxv' size='340' side='right'caption='[[1kxv]], [[Resolution|resolution]] 1.60Å' scene=''> | |||
You may | == Structural highlights == | ||
<table><tr><td colspan='2'>[[1kxv]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Camelus_dromedarius Camelus dromedarius] and [https://en.wikipedia.org/wiki/Sus_scrofa Sus scrofa]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1KXV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1KXV FirstGlance]. <br> | |||
or | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.6Å</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=1kxv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1kxv OCA], [https://pdbe.org/1kxv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1kxv RCSB], [https://www.ebi.ac.uk/pdbsum/1kxv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1kxv ProSAT]</span></td></tr> | ||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/AMYP_PIG AMYP_PIG] | |||
== 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/kx/1kxv_consurf.spt"</scriptWhenChecked> | |||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.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=1kxv ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Camelids produce functional antibodies devoid of light chains and CH1 domains. The antigen-binding fragment of such heavy chain antibodies is therefore comprised in one single domain, the camelid heavy chain antibody VH (VHH). Here we report on the structures of three dromedary VHH domains in complex with porcine pancreatic alpha-amylase. Two VHHs bound outside the catalytic site and did not inhibit or inhibited only partially the amylase activity. The third one, AMD9, interacted with the active site crevice and was a strong amylase inhibitor (K(i) = 10 nm). In contrast with complexes of other proteinaceous amylase inhibitors, amylase kept its native structure. The water-accessible surface areas of VHHs covered by amylase ranged between 850 and 1150 A(2), values similar to or even larger than those observed in the complexes between proteins and classical antibodies. These values could certainly be reached because a surprisingly high extent of framework residues are involved in the interactions of VHHs with amylase. The framework residues that participate in the antigen recognition represented 25-40% of the buried surface. The inhibitory interaction of AMD9 involved mainly its complementarity-determining region (CDR) 2 loop, whereas the CDR3 loop was small and certainly did not protrude as it does in cAb-Lys3, a VHH-inhibiting lysozyme. AMD9 inhibited amylase, although it was outside the direct reach of the catalytic residues; therefore it is to be expected that inhibiting VHHs might also be elicited against proteases. These results illustrate the versatility and efficiency of VHH domains as protein binders and enzyme inhibitors and are arguments in favor of their use as drugs against diabetes. | |||
Three camelid VHH domains in complex with porcine pancreatic alpha-amylase. Inhibition and versatility of binding topology.,Desmyter A, Spinelli S, Payan F, Lauwereys M, Wyns L, Muyldermans S, Cambillau C J Biol Chem. 2002 Jun 28;277(26):23645-50. Epub 2002 Apr 17. PMID:11960990<ref>PMID:11960990</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 1kxv" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Amylase 3D structures|Amylase 3D structures]] | |||
*[[Antibody 3D structures|Antibody 3D structures]] | |||
*[[3D structures of non-human antibody|3D structures of non-human antibody]] | |||
== References == | |||
<references/> | |||
== | __TOC__ | ||
</StructureSection> | |||
== | |||
< | |||
[[Category: Camelus dromedarius]] | [[Category: Camelus dromedarius]] | ||
[[Category: Large Structures]] | |||
[[Category: Sus scrofa]] | [[Category: Sus scrofa]] | ||
[[Category: Cambillau | [[Category: Cambillau C]] | ||
[[Category: Desmyter | [[Category: Desmyter A]] | ||
[[Category: Lauwereys | [[Category: Lauwereys M]] | ||
[[Category: Muyldermans | [[Category: Muyldermans S]] | ||
[[Category: Payan | [[Category: Payan F]] | ||
[[Category: Spinelli | [[Category: Spinelli S]] | ||
[[Category: Wyns | [[Category: Wyns L]] | ||
Latest revision as of 11:36, 6 November 2024
Camelid VHH Domains in Complex with Porcine Pancreatic alpha-AmylaseCamelid VHH Domains in Complex with Porcine Pancreatic alpha-Amylase
Structural highlights
FunctionEvolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedCamelids produce functional antibodies devoid of light chains and CH1 domains. The antigen-binding fragment of such heavy chain antibodies is therefore comprised in one single domain, the camelid heavy chain antibody VH (VHH). Here we report on the structures of three dromedary VHH domains in complex with porcine pancreatic alpha-amylase. Two VHHs bound outside the catalytic site and did not inhibit or inhibited only partially the amylase activity. The third one, AMD9, interacted with the active site crevice and was a strong amylase inhibitor (K(i) = 10 nm). In contrast with complexes of other proteinaceous amylase inhibitors, amylase kept its native structure. The water-accessible surface areas of VHHs covered by amylase ranged between 850 and 1150 A(2), values similar to or even larger than those observed in the complexes between proteins and classical antibodies. These values could certainly be reached because a surprisingly high extent of framework residues are involved in the interactions of VHHs with amylase. The framework residues that participate in the antigen recognition represented 25-40% of the buried surface. The inhibitory interaction of AMD9 involved mainly its complementarity-determining region (CDR) 2 loop, whereas the CDR3 loop was small and certainly did not protrude as it does in cAb-Lys3, a VHH-inhibiting lysozyme. AMD9 inhibited amylase, although it was outside the direct reach of the catalytic residues; therefore it is to be expected that inhibiting VHHs might also be elicited against proteases. These results illustrate the versatility and efficiency of VHH domains as protein binders and enzyme inhibitors and are arguments in favor of their use as drugs against diabetes. Three camelid VHH domains in complex with porcine pancreatic alpha-amylase. Inhibition and versatility of binding topology.,Desmyter A, Spinelli S, Payan F, Lauwereys M, Wyns L, Muyldermans S, Cambillau C J Biol Chem. 2002 Jun 28;277(26):23645-50. Epub 2002 Apr 17. PMID:11960990[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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