2hw1: Difference between revisions

Latest revision as of 10:02, 30 August 2023

Crystal structure of human ketohexokinase complexed to different sugar molecules

Structural highlights

2hw1 is a 1 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 2.1Å
Ligands:	ANP, FRU, GOL, SO4
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

KHK_HUMAN Defects in KHK are the cause of fructosuria (FRUCT) [MIM:229800. Benign defect of intermediary metabolism.^[1] ^[2]

Function

KHK_HUMAN

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

A molecular understanding of the unique aspects of dietary fructose metabolism may be the key to understanding and controlling the current epidemic of fructose-related obesity, diabetes and related adverse metabolic states in Western populations. Fructose catabolism is initiated by its phosphorylation to fructose 1-phosphate, which is performed by ketohexokinase (KHK). Here, the crystal structures of the two alternatively spliced isoforms of human ketohexokinase, hepatic KHK-C and the peripheral isoform KHK-A, and of the ternary complex of KHK-A with the substrate fructose and AMP-PNP are reported. The structure of the KHK-A ternary complex revealed an active site with both the substrate fructose and the ATP analogue in positions ready for phosphorylation following a reaction mechanism similar to that of the pfkB family of carbohydrate kinases. Hepatic KHK deficiency causes the benign disorder essential fructosuria. The effects of the disease-causing mutations (Gly40Arg and Ala43Thr) have been modelled in the context of the KHK structure.

Structures of alternatively spliced isoforms of human ketohexokinase.,Trinh CH, Asipu A, Bonthron DT, Phillips SE Acta Crystallogr D Biol Crystallogr. 2009 Mar;65(Pt 3):201-11. Epub 2009, Feb 20. PMID:19237742^[3]

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

References

↑ Trinh CH, Asipu A, Bonthron DT, Phillips SE. Structures of alternatively spliced isoforms of human ketohexokinase. Acta Crystallogr D Biol Crystallogr. 2009 Mar;65(Pt 3):201-11. Epub 2009, Feb 20. PMID:19237742 doi:S0907444908041115
↑ Bonthron DT, Brady N, Donaldson IA, Steinmann B. Molecular basis of essential fructosuria: molecular cloning and mutational analysis of human ketohexokinase (fructokinase). Hum Mol Genet. 1994 Sep;3(9):1627-31. PMID:7833921
↑ Trinh CH, Asipu A, Bonthron DT, Phillips SE. Structures of alternatively spliced isoforms of human ketohexokinase. Acta Crystallogr D Biol Crystallogr. 2009 Mar;65(Pt 3):201-11. Epub 2009, Feb 20. PMID:19237742 doi:S0907444908041115

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OCA

[1] Trinh CH, Asipu A, Bonthron DT, Phillips SE. Structures of alternatively spliced isoforms of human ketohexokinase. Acta Crystallogr D Biol Crystallogr. 2009 Mar;65(Pt 3):201-11. Epub 2009, Feb 20. PMID:19237742 doi:S0907444908041115

[2] Bonthron DT, Brady N, Donaldson IA, Steinmann B. Molecular basis of essential fructosuria: molecular cloning and mutational analysis of human ketohexokinase (fructokinase). Hum Mol Genet. 1994 Sep;3(9):1627-31. PMID:7833921

[3] Trinh CH, Asipu A, Bonthron DT, Phillips SE. Structures of alternatively spliced isoforms of human ketohexokinase. Acta Crystallogr D Biol Crystallogr. 2009 Mar;65(Pt 3):201-11. Epub 2009, Feb 20. PMID:19237742 doi:S0907444908041115

[1]

[2]

[3]

@@ Line 3: / Line 3: @@
 <StructureSection load='2hw1' size='340' side='right'caption='[[2hw1]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[2hw1]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2HW1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2HW1 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[2hw1]] is a 1 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=2HW1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2HW1 FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ANP:PHOSPHOAMINOPHOSPHONIC+ACID-ADENYLATE+ESTER'>ANP</scene>, <scene name='pdbligand=FRU:FRUCTOSE'>FRU</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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]] 2.1&#8491;</td></tr>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2hqq|2hqq]]</div></td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ANP:PHOSPHOAMINOPHOSPHONIC+ACID-ADENYLATE+ESTER'>ANP</scene>, <scene name='pdbligand=FRU:FRUCTOSE'>FRU</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">KHK ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
-<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Ketohexokinase Ketohexokinase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.3 2.7.1.3] </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=2hw1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2hw1 OCA], [https://pdbe.org/2hw1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2hw1 RCSB], [https://www.ebi.ac.uk/pdbsum/2hw1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2hw1 ProSAT]</span></td></tr>
 </table>
 == Disease ==
-[[https://www.uniprot.org/uniprot/KHK_HUMAN KHK_HUMAN]] Defects in KHK are the cause of fructosuria (FRUCT) [MIM:[https://omim.org/entry/229800 229800]]. Benign defect of intermediary metabolism.<ref>PMID:19237742</ref> <ref>PMID:7833921</ref>
+[https://www.uniprot.org/uniprot/KHK_HUMAN KHK_HUMAN] Defects in KHK are the cause of fructosuria (FRUCT) [MIM:[https://omim.org/entry/229800 229800]. Benign defect of intermediary metabolism.<ref>PMID:19237742</ref> <ref>PMID:7833921</ref>
+== Function ==
+[https://www.uniprot.org/uniprot/KHK_HUMAN KHK_HUMAN]
 == Evolutionary Conservation ==
 [[Image:Consurf_key_small.gif|200px|right]]
@@ Line 38: / Line 38: @@
 __TOC__
 </StructureSection>
-[[Category: Human]]
+[[Category: Homo sapiens]]
-[[Category: Ketohexokinase]]
 [[Category: Large Structures]]
-[[Category: Asipu, A]]
+[[Category: Asipu A]]
-[[Category: Bonthron, D T]]
+[[Category: Bonthron DT]]
-[[Category: Phillips, S E.V]]
+[[Category: Phillips SEV]]
-[[Category: Trinh, C H]]
+[[Category: Trinh CH]]
-[[Category: Fructose kinase]]
-[[Category: Transferase]]

2hw1: Difference between revisions

Latest revision as of 10:02, 30 August 2023

Crystal structure of human ketohexokinase complexed to different sugar molecules

Structural highlights

Disease

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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