7s4c: Difference between revisions

From Proteopedia
Jump to navigation Jump to search
← Older edit
No edit summary
No edit summary
 
Line 3: Line 3:
<StructureSection load='7s4c' size='340' side='right'caption='[[7s4c]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
<StructureSection load='7s4c' size='340' side='right'caption='[[7s4c]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[7s4c]] 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=7S4C OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7S4C FirstGlance]. <br>
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7S4C OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7S4C FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.2&#8491;</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]] 2.2&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GLA:ALPHA+D-GALACTOSE'>GLA</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene>, <scene name='pdbligand=V3V:2-({(4R)-4-(2-chlorophenyl)-2-[(6-fluoro-1,3-benzoxazol-2-yl)amino]-6-methyl-1,4-dihydropyrimidine-5-carbonyl}amino)pyridine-4-carboxylic+acid'>V3V</scene></td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GLA:ALPHA+D-GALACTOSE'>GLA</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene>, <scene name='pdbligand=V3V:2-({(4R)-4-(2-chlorophenyl)-2-[(6-fluoro-1,3-benzoxazol-2-yl)amino]-6-methyl-1,4-dihydropyrimidine-5-carbonyl}amino)pyridine-4-carboxylic+acid'>V3V</scene></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=7s4c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7s4c OCA], [https://pdbe.org/7s4c PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7s4c RCSB], [https://www.ebi.ac.uk/pdbsum/7s4c PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7s4c ProSAT]</span></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=7s4c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7s4c OCA], [https://pdbe.org/7s4c PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7s4c RCSB], [https://www.ebi.ac.uk/pdbsum/7s4c PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7s4c ProSAT]</span></td></tr>
</table>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/GALK1_HUMAN GALK1_HUMAN] Defects in GALK1 are the cause of galactosemia II (GALCT2) [MIM:[https://omim.org/entry/230200 230200]. Galactosemia II is an autosomal recessive deficiency characterized by congenital cataracts during infancy and presenile cataracts in the adult population. The cataracts are secondary to accumulation of galactitol in the lenses.<ref>PMID:10521295</ref> <ref>PMID:10790206</ref> <ref>PMID:11231902</ref> <ref>PMID:11139256</ref> <ref>PMID:12694189</ref> <ref>PMID:15024738</ref>
== Function ==
[https://www.uniprot.org/uniprot/GALK1_HUMAN GALK1_HUMAN] Major enzyme for galactose metabolism.
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Classic galactosemia is a rare disease caused by inherited deficiency of galactose-1 phosphate uridylyltransferase (GALT). Accumulation of galactose-1 phosphate (gal-1P) is thought to be the major cause of the chronic complications associated with this disease, which currently has no treatment. Inhibiting galactokinase (GALK1), the enzyme that generates galactose-1 phosphate, has been proposed as a novel strategy for treating classic galactosemia. Our previous work identified a highly selective unique dihydropyrimidine inhibitor against GALK1. With the determination of a co-crystal structure of this inhibitor with human GALK1, we initiated a structure-based structure-activity relationship (SAR) optimization campaign that yielded novel analogs with potent biochemical inhibition (IC50 &lt; 100 nM). Lead compounds were also able to prevent gal-1P accumulation in patient-derived cells at low micromolar concentrations and have pharmacokinetic properties suitable for evaluation in rodent models of galactosemia.
Structure-Based Optimization of Small Molecule Human Galactokinase Inhibitors.,Liu L, Tang M, Pragani R, Whitby FG, Zhang YQ, Balakrishnan B, Fang Y, Karavadhi S, Tao D, LeClair CA, Hall MD, Marugan JJ, Boxer M, Shen M, Hill CP, Lai K, Patnaik S J Med Chem. 2021 Sep 23;64(18):13551-13571. doi: 10.1021/acs.jmedchem.1c00945., Epub 2021 Sep 7. PMID:34491744<ref>PMID:34491744</ref>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7s4c" style="background-color:#fffaf0;"></div>


==See Also==
==See Also==
*[[Galactokinase|Galactokinase]]
*[[Galactokinase|Galactokinase]]
== References ==
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Large Structures]]
[[Category: Whitby FG]]
[[Category: Whitby FG]]

Latest revision as of 12:09, 17 October 2024

Crystal Structure of Inhibitor-bound GalactokinaseCrystal Structure of Inhibitor-bound Galactokinase

Structural highlights

Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.2Å
Ligands:, , ,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

See Also

7s4c, resolution 2.20Å

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA
Retrieved from "https://proteopedia.openfox.io/wiki/index.php?title=7s4c&oldid=4232355"