2bkk

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Current revision (10:53, 6 April 2022) (edit) (undo)
 
(13 intermediate revisions not shown.)
Line 1: Line 1:
-
[[Image:2bkk.gif|left|200px]]
 
-
{{Structure
+
==Crystal structure of Aminoglycoside Phosphotransferase APH(3')-IIIa in complex with the inhibitor AR_3a==
-
|PDB= 2bkk |SIZE=350|CAPTION= <scene name='initialview01'>2bkk</scene>, resolution 2.15&Aring;
+
<StructureSection load='2bkk' size='340' side='right'caption='[[2bkk]], [[Resolution|resolution]] 2.15&Aring;' scene=''>
-
|SITE= <scene name='pdbsite=AC1:Mg+Binding+Site+For+Chain+C'>AC1</scene>
+
== Structural highlights ==
-
|LIGAND= <scene name='pdbligand=ADP:ADENOSINE-5&#39;-DIPHOSPHATE'>ADP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>
+
<table><tr><td colspan='2'>[[2bkk]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/"enterococcus_proteiformis"_thiercelin_and_jouhaud_1903 "enterococcus proteiformis" thiercelin and jouhaud 1903] and [https://en.wikipedia.org/wiki/Synthetic_construct_sequences Synthetic construct sequences]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2BKK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2BKK FirstGlance]. <br>
-
|ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/Kanamycin_kinase Kanamycin kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.95 2.7.1.95] </span>
+
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>
-
|GENE=
+
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1k1a|1k1a]], [[1k1b|1k1b]], [[1mj0|1mj0]], [[1n0q|1n0q]], [[1n0r|1n0r]], [[1j7i|1j7i]], [[1j7l|1j7l]], [[1j7u|1j7u]], [[1l8t|1l8t]], [[1l8u|1l8u]], [[2bkg|2bkg]]</div></td></tr>
-
|DOMAIN=
+
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Kanamycin_kinase Kanamycin kinase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.95 2.7.1.95] </span></td></tr>
-
|RELATEDENTRY=
+
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2bkk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2bkk OCA], [https://pdbe.org/2bkk PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2bkk RCSB], [https://www.ebi.ac.uk/pdbsum/2bkk PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2bkk ProSAT]</span></td></tr>
-
|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2bkk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2bkk OCA], [http://www.ebi.ac.uk/pdbsum/2bkk PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2bkk RCSB]</span>
+
</table>
-
}}
+
== Function ==
 +
[[https://www.uniprot.org/uniprot/KKA3_ENTFL KKA3_ENTFL]] Resistance to kanamycin and structurally-related aminoglycosides, including amikacin.
 +
== 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/bk/2bkk_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=2bkk ConSurf].
 +
<div style="clear:both"></div>
 +
<div style="background-color:#fffaf0;">
 +
== Publication Abstract from PubMed ==
 +
Aminoglycoside phosphotransferase (3')-IIIa (APH) is a bacterial kinase that confers antibiotic resistance to many pathogenic bacteria and shares structural homology with eukaryotic protein kinases. We report here the crystal structure of APH, trapped in an inactive conformation by a tailor-made inhibitory ankyrin repeat (AR) protein, at 2.15 A resolution. The inhibitor was selected from a combinatorial library of designed AR proteins. The AR protein binds the C-terminal lobe of APH and thereby stabilizes three alpha helices, which are necessary for substrate binding, in a significantly displaced conformation. BIAcore analysis and kinetic enzyme inhibition experiments are consistent with the proposed allosteric inhibition mechanism. In contrast to most small-molecule kinase inhibitors, the AR proteins are not restricted to active site binding, allowing for higher specificity. Inactive conformations of pharmaceutically relevant enzymes, as can be elucidated with the approach presented here, represent powerful starting points for rational drug design.
-
'''CRYSTAL STRUCTURE OF AMINOGLYCOSIDE PHOSPHOTRANSFERASE APH (3')-IIIA IN COMPLEX WITH THE INHIBITOR AR_3A'''
+
Allosteric inhibition of aminoglycoside phosphotransferase by a designed ankyrin repeat protein.,Kohl A, Amstutz P, Parizek P, Binz HK, Briand C, Capitani G, Forrer P, Pluckthun A, Grutter MG Structure. 2005 Aug;13(8):1131-41. PMID:16084385<ref>PMID:16084385</ref>
 +
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 +
</div>
 +
<div class="pdbe-citations 2bkk" style="background-color:#fffaf0;"></div>
-
==Overview==
+
==See Also==
-
Aminoglycoside phosphotransferase (3')-IIIa (APH) is a bacterial kinase that confers antibiotic resistance to many pathogenic bacteria and shares structural homology with eukaryotic protein kinases. We report here the crystal structure of APH, trapped in an inactive conformation by a tailor-made inhibitory ankyrin repeat (AR) protein, at 2.15 A resolution. The inhibitor was selected from a combinatorial library of designed AR proteins. The AR protein binds the C-terminal lobe of APH and thereby stabilizes three alpha helices, which are necessary for substrate binding, in a significantly displaced conformation. BIAcore analysis and kinetic enzyme inhibition experiments are consistent with the proposed allosteric inhibition mechanism. In contrast to most small-molecule kinase inhibitors, the AR proteins are not restricted to active site binding, allowing for higher specificity. Inactive conformations of pharmaceutically relevant enzymes, as can be elucidated with the approach presented here, represent powerful starting points for rational drug design.
+
*[[Phosphotransferase 3D structures|Phosphotransferase 3D structures]]
-
 
+
== References ==
-
==About this Structure==
+
<references/>
-
2BKK is a [[Protein complex]] structure of sequences from [http://en.wikipedia.org/wiki/Enterococcus_faecalis Enterococcus faecalis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2BKK OCA].
+
__TOC__
-
 
+
</StructureSection>
-
==Reference==
+
[[Category: Enterococcus proteiformis thiercelin and jouhaud 1903]]
-
Allosteric inhibition of aminoglycoside phosphotransferase by a designed ankyrin repeat protein., Kohl A, Amstutz P, Parizek P, Binz HK, Briand C, Capitani G, Forrer P, Pluckthun A, Grutter MG, Structure. 2005 Aug;13(8):1131-41. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/16084385 16084385]
+
-
[[Category: Enterococcus faecalis]]
+
[[Category: Kanamycin kinase]]
[[Category: Kanamycin kinase]]
-
[[Category: Protein complex]]
+
[[Category: Large Structures]]
-
[[Category: Amstutz, P.]]
+
[[Category: Synthetic construct sequences]]
-
[[Category: Binz, H K.]]
+
[[Category: Amstutz, P]]
-
[[Category: Briand, C.]]
+
[[Category: Binz, H K]]
-
[[Category: Capitani, G.]]
+
[[Category: Briand, C]]
-
[[Category: Forrer, P.]]
+
[[Category: Capitani, G]]
-
[[Category: Grutter, M G.]]
+
[[Category: Forrer, P]]
-
[[Category: Kohl, A.]]
+
[[Category: Grutter, M G]]
-
[[Category: Parizek, P.]]
+
[[Category: Kohl, A]]
-
[[Category: Pluckthun, A.]]
+
[[Category: Parizek, P]]
-
[[Category: ankyrin repeat]]
+
[[Category: Pluckthun, A]]
-
[[Category: antibiotic resistance]]
+
[[Category: Ankyrin repeat]]
-
[[Category: atp-binding]]
+
[[Category: Antibiotic resistance]]
-
[[Category: co-crystallization]]
+
[[Category: Atp-binding]]
-
[[Category: designed repeat protein]]
+
[[Category: Co-crystallization]]
-
[[Category: drug design]]
+
[[Category: Designed repeat protein]]
-
[[Category: enzyme inhibition]]
+
[[Category: Drug design]]
-
[[Category: inhibitor design]]
+
[[Category: Enzyme inhibition]]
-
[[Category: kinase]]
+
[[Category: Inhibitor design]]
-
[[Category: kinase inhibition]]
+
[[Category: Kinase]]
-
[[Category: plasmid]]
+
[[Category: Kinase inhibition]]
-
[[Category: transferase]]
+
[[Category: Plasmid]]
-
 
+
[[Category: Transferase]]
-
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 02:07:47 2008''
+
[[Category: Transferase-designed protein complex]]
 +
[[Category: Transferase-peptide complex]]
 +
[[Category: Transferase/peptide]]

Current revision

Crystal structure of Aminoglycoside Phosphotransferase APH(3')-IIIa in complex with the inhibitor AR_3a

PDB ID 2bkk

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2bkk"
Personal tools