5bwv

From Proteopedia

(Difference between revisions)

Current revision

X-RAY CRYSTAL STRUCTURE AT 1.86A RESOLUTION OF HUMAN MITOCHONDRIAL BRANCHED CHAIN AMINOTRANSFERASE (BCATM) COMPLEXED WITH A PYRAZOLOPYRIMIDINONE COMPOUND AND AN INTERNAL ALDIMINE LINKED PLP COFACTOR.

Structural highlights

5bwv is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.86Å
Ligands:	, , , ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

BCAT2_HUMAN Catalyzes the first reaction in the catabolism of the essential branched chain amino acids leucine, isoleucine, and valine. May also function as a transporter of branched chain alpha-keto acids.

Publication Abstract from PubMed

The hybridisation of hits, identified by complementary fragment and high throughput screens, enabled the discovery of the first series of potent inhibitors of mitochondrial branched-chain aminotransferase (BCATm), based on a 2-benzylamino-pyrazolo[1,5-a]pyrimidinone-3-carbonitrile template. Structure-guided growth enabled rapid optimisation of activity with maintenance of ligand efficiency, whilst the focus on physical properties delivered compounds with excellent pharmacokinetic exposure that enabled an acute proof of concept experiment in mice. Oral administration of 2-((4-chloro-2,6-difluorobenzyl)amino)-7-oxo-5-propyl-4,7-dihydropyrazolo[1,5-a]p yrimidine-3-carbonitrile 61 significantly raised the circulating levels of the branched-chain amino acids leucine, isoleucine and valine in this acute study.

The discovery of in vivo active mitochondrial branched-chain aminotransferase (BCATm) inhibitors by hybridising fragment and HTS hits.,Bertrand SM, Ancellin N, Beaufils B, Bingham RP, Borthwick JA, Boullay AB, Boursier E, Carter PS, Chung CW, Churcher I, Dodic N, Fouchet MH, Fournier C, Francis P, Gummer LA, Herry K, Hobbs A, Hobbs CI, Homes P, Jamieson C, Nicodeme E, Pickett SD, Reid IH, Simpson GL, Sloan LA, Smith SE, Somers DO, Spitzfaden C, Suckling CJ, Valko K, Washio Y, Young RJ J Med Chem. 2015 Jun 19. PMID:26090771^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Bertrand SM, Ancellin N, Beaufils B, Bingham RP, Borthwick JA, Boullay AB, Boursier E, Carter PS, Chung CW, Churcher I, Dodic N, Fouchet MH, Fournier C, Francis P, Gummer LA, Herry K, Hobbs A, Hobbs CI, Homes P, Jamieson C, Nicodeme E, Pickett SD, Reid IH, Simpson GL, Sloan LA, Smith SE, Somers DO, Spitzfaden C, Suckling CJ, Valko K, Washio Y, Young RJ. The discovery of in vivo active mitochondrial branched-chain aminotransferase (BCATm) inhibitors by hybridising fragment and HTS hits. J Med Chem. 2015 Jun 19. PMID:26090771 doi:http://dx.doi.org/10.1021/acs.jmedchem.5b00313

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5bwv"

Categories: Homo sapiens | Large Structures | Somers DO

@@ Line 3: / Line 3: @@
 <StructureSection load='5bwv' size='340' side='right'caption='[[5bwv]], [[Resolution|resolution]] 1.86&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5bwv]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5BWV OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5BWV FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5bwv]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5BWV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5BWV FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=775:2-[(4-CHLOROBENZYL)AMINO]-7-OXO-5-PROPYL-4,7-DIHYDROPYRAZOLO[1,5-A]PYRIMIDINE-3-CARBONITRILE'>775</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=PLP:PYRIDOXAL-5-PHOSPHATE'>PLP</scene></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.86&#8491;</td></tr>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5bwr|5bwr]], [[5bwt|5bwt]], [[5bwu|5bwu]]</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=775:2-[(4-CHLOROBENZYL)AMINO]-7-OXO-5-PROPYL-4,7-DIHYDROPYRAZOLO[1,5-A]PYRIMIDINE-3-CARBONITRILE'>775</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=PLP:PYRIDOXAL-5-PHOSPHATE'>PLP</scene></td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">BCAT2, BCATM, BCT2, ECA40 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=5bwv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5bwv OCA], [https://pdbe.org/5bwv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5bwv RCSB], [https://www.ebi.ac.uk/pdbsum/5bwv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5bwv ProSAT]</span></td></tr>
-<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Branched-chain-amino-acid_transaminase Branched-chain-amino-acid transaminase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.6.1.42 2.6.1.42] </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=5bwv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5bwv OCA], [http://pdbe.org/5bwv PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5bwv RCSB], [http://www.ebi.ac.uk/pdbsum/5bwv PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5bwv ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[http://www.uniprot.org/uniprot/BCAT2_HUMAN BCAT2_HUMAN]] Catalyzes the first reaction in the catabolism of the essential branched chain amino acids leucine, isoleucine, and valine. May also function as a transporter of branched chain alpha-keto acids.
+[https://www.uniprot.org/uniprot/BCAT2_HUMAN BCAT2_HUMAN] Catalyzes the first reaction in the catabolism of the essential branched chain amino acids leucine, isoleucine, and valine. May also function as a transporter of branched chain alpha-keto acids.
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 28: / Line 26: @@
 __TOC__
 </StructureSection>
-[[Category: Branched-chain-amino-acid transaminase]]
+[[Category: Homo sapiens]]
-[[Category: Human]]
 [[Category: Large Structures]]
-[[Category: Somers, D O]]
+[[Category: Somers DO]]
-[[Category: Fold type iv]]
-[[Category: Transferase]]

5bwv

From Proteopedia

Current revision

X-RAY CRYSTAL STRUCTURE AT 1.86A RESOLUTION OF HUMAN MITOCHONDRIAL BRANCHED CHAIN AMINOTRANSFERASE (BCATM) COMPLEXED WITH A PYRAZOLOPYRIMIDINONE COMPOUND AND AN INTERNAL ALDIMINE LINKED PLP COFACTOR.

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

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