1cza
From Proteopedia
(New page: 200px<br /> <applet load="1cza" size="450" color="white" frame="true" align="right" spinBox="true" caption="1cza, resolution 1.9Å" /> '''MUTANT MONOMER OF RE...) |
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| - | [[Image:1cza.gif|left|200px]]<br /> | + | [[Image:1cza.gif|left|200px]]<br /><applet load="1cza" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1cza" size=" | + | |
caption="1cza, resolution 1.9Å" /> | caption="1cza, resolution 1.9Å" /> | ||
'''MUTANT MONOMER OF RECOMBINANT HUMAN HEXOKINASE TYPE I COMPLEXED WITH GLUCOSE, GLUCOSE-6-PHOSPHATE, AND ADP'''<br /> | '''MUTANT MONOMER OF RECOMBINANT HUMAN HEXOKINASE TYPE I COMPLEXED WITH GLUCOSE, GLUCOSE-6-PHOSPHATE, AND ADP'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Hexokinase I, the pacemaker of glycolysis in brain tissue, is composed of | + | Hexokinase I, the pacemaker of glycolysis in brain tissue, is composed of two structurally similar halves connected by an alpha-helix. The enzyme dimerizes at elevated protein concentrations in solution and in crystal structures; however, almost all published data reflect the properties of a hexokinase I monomer in solution. Crystal structures of mutant forms of recombinant human hexokinase I, presented here, reveal the enzyme monomer for the first time. The mutant hexokinases bind both glucose 6-phosphate and glucose with high affinity to their N and C-terminal halves, and ADP, also with high affinity, to a site near the N terminus of the polypeptide chain. Exposure of the monomer crystals to ADP in the complete absence of glucose 6-phosphate reveals a second binding site for adenine nucleotides at the putative active site (C-half), with conformational changes extending 15 A to the contact interface between the N and C-halves. The structures reveal distinct conformational states for the C-half and a rigid-body rotation of the N-half, as possible elements of a structure-based mechanism for allosteric regulation of catalysis. |
==Disease== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1CZA is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with GLC, G6P and ADP as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Hexokinase Hexokinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.1 2.7.1.1] Full crystallographic information is available from [http:// | + | 1CZA is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=GLC:'>GLC</scene>, <scene name='pdbligand=G6P:'>G6P</scene> and <scene name='pdbligand=ADP:'>ADP</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Hexokinase Hexokinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.1 2.7.1.1] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1CZA OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Aleshin, A | + | [[Category: Aleshin, A E.]] |
| - | [[Category: Bartunik, H | + | [[Category: Bartunik, H D.]] |
| - | [[Category: Bourenkov, G | + | [[Category: Bourenkov, G P.]] |
| - | [[Category: Fromm, H | + | [[Category: Fromm, H J.]] |
| - | [[Category: Honzatko, R | + | [[Category: Honzatko, R B.]] |
[[Category: Kirby, C.]] | [[Category: Kirby, C.]] | ||
[[Category: Liu, X.]] | [[Category: Liu, X.]] | ||
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[[Category: structurally homologous domains]] | [[Category: structurally homologous domains]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:11:13 2008'' |
Revision as of 10:11, 21 February 2008
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MUTANT MONOMER OF RECOMBINANT HUMAN HEXOKINASE TYPE I COMPLEXED WITH GLUCOSE, GLUCOSE-6-PHOSPHATE, AND ADP
Contents |
Overview
Hexokinase I, the pacemaker of glycolysis in brain tissue, is composed of two structurally similar halves connected by an alpha-helix. The enzyme dimerizes at elevated protein concentrations in solution and in crystal structures; however, almost all published data reflect the properties of a hexokinase I monomer in solution. Crystal structures of mutant forms of recombinant human hexokinase I, presented here, reveal the enzyme monomer for the first time. The mutant hexokinases bind both glucose 6-phosphate and glucose with high affinity to their N and C-terminal halves, and ADP, also with high affinity, to a site near the N terminus of the polypeptide chain. Exposure of the monomer crystals to ADP in the complete absence of glucose 6-phosphate reveals a second binding site for adenine nucleotides at the putative active site (C-half), with conformational changes extending 15 A to the contact interface between the N and C-halves. The structures reveal distinct conformational states for the C-half and a rigid-body rotation of the N-half, as possible elements of a structure-based mechanism for allosteric regulation of catalysis.
Disease
Known disease associated with this structure: Hemolytic anemia due to hexokinase deficiency OMIM:[142600]
About this Structure
1CZA is a Single protein structure of sequence from Homo sapiens with , and as ligands. Active as Hexokinase, with EC number 2.7.1.1 Full crystallographic information is available from OCA.
Reference
Crystal structures of mutant monomeric hexokinase I reveal multiple ADP binding sites and conformational changes relevant to allosteric regulation., Aleshin AE, Kirby C, Liu X, Bourenkov GP, Bartunik HD, Fromm HJ, Honzatko RB, J Mol Biol. 2000 Mar 3;296(4):1001-15. PMID:10686099
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