1a05
From Proteopedia
(New page: 200px<br /><applet load="1a05" size="450" color="white" frame="true" align="right" spinBox="true" caption="1a05, resolution 2.00Å" /> '''CRYSTAL STRUCTURE OF...) |
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| - | [[Image:1a05.gif|left|200px]]<br /><applet load="1a05" size=" | + | [[Image:1a05.gif|left|200px]]<br /><applet load="1a05" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1a05, resolution 2.00Å" /> | caption="1a05, resolution 2.00Å" /> | ||
'''CRYSTAL STRUCTURE OF THE COMPLEX OF 3-ISOPROPYLMALATE DEHYDROGENASE FROM THIOBACILLUS FERROOXIDANS WITH 3-ISOPROPYLMALATE'''<br /> | '''CRYSTAL STRUCTURE OF THE COMPLEX OF 3-ISOPROPYLMALATE DEHYDROGENASE FROM THIOBACILLUS FERROOXIDANS WITH 3-ISOPROPYLMALATE'''<br /> | ||
==Overview== | ==Overview== | ||
| - | BACKGROUND: 3-Isopropylmalate dehydrogenase (IPMDH) and isocitrate | + | BACKGROUND: 3-Isopropylmalate dehydrogenase (IPMDH) and isocitrate dehydrogenase (ICDH) belong to a unique family of bifunctional decarboxylating dehydrogenases. Although the ICDH dimer catalyzes its reaction under a closed conformation, known structures of the IPMDH dimer (without substrate) adopt a fully open or a partially closed form. Considering the similarity in the catalytic mechanism, the IPMDH dimer must be in a fully closed conformation during the reaction. A large conformational change should therefore occur upon substrate binding. RESULTS: We have determined the crystal structure of IPMDH from Thiobacillus ferrooxidans (Tf) complexed with 3-isopropylmalate (IPM) at 2.0 A resolution by the molecular replacement method. The structure shows a fully closed conformation and the substrate-binding site is quite similar to that of ICDH except for a region around the gamma-isopropyl group. The gamma group is recognized by a unique hydrophobic pocket, which includes Glu88, Leu91 and Leu92 from subunit 1 and Val193' from subunit 2. CONCLUSIONS: A large movement of domain 1 is induced by substrate binding, which results in the formation of the hydrophobic pocket for the gamma-isopropyl moiety of IPM. A glutamic acid in domain 1, Glu88, participates in the formation of the hydrophobic pocket. The C beta and C gamma atoms of Glu88 interact with the gamma-isopropyl moiety of IPM and are central to the recognition of substrate. The acidic tip of Glu88 is likely to interact with the nicotinamide mononucleotide (NMN) ribose of NAD+ in the ternary complex. This structure clearly explains the substrate specificity of IPMDH. |
==About this Structure== | ==About this Structure== | ||
| - | 1A05 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Acidithiobacillus_ferrooxidans Acidithiobacillus ferrooxidans] with MG and IPM as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/3-isopropylmalate_dehydrogenase 3-isopropylmalate dehydrogenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.1.1.85 1.1.1.85] Full crystallographic information is available from [http:// | + | 1A05 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Acidithiobacillus_ferrooxidans Acidithiobacillus ferrooxidans] with <scene name='pdbligand=MG:'>MG</scene> and <scene name='pdbligand=IPM:'>IPM</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/3-isopropylmalate_dehydrogenase 3-isopropylmalate dehydrogenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.1.1.85 1.1.1.85] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1A05 OCA]. |
==Reference== | ==Reference== | ||
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[[Category: oxidoreductase]] | [[Category: oxidoreductase]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 11:39:24 2008'' |
Revision as of 09:39, 21 February 2008
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CRYSTAL STRUCTURE OF THE COMPLEX OF 3-ISOPROPYLMALATE DEHYDROGENASE FROM THIOBACILLUS FERROOXIDANS WITH 3-ISOPROPYLMALATE
Overview
BACKGROUND: 3-Isopropylmalate dehydrogenase (IPMDH) and isocitrate dehydrogenase (ICDH) belong to a unique family of bifunctional decarboxylating dehydrogenases. Although the ICDH dimer catalyzes its reaction under a closed conformation, known structures of the IPMDH dimer (without substrate) adopt a fully open or a partially closed form. Considering the similarity in the catalytic mechanism, the IPMDH dimer must be in a fully closed conformation during the reaction. A large conformational change should therefore occur upon substrate binding. RESULTS: We have determined the crystal structure of IPMDH from Thiobacillus ferrooxidans (Tf) complexed with 3-isopropylmalate (IPM) at 2.0 A resolution by the molecular replacement method. The structure shows a fully closed conformation and the substrate-binding site is quite similar to that of ICDH except for a region around the gamma-isopropyl group. The gamma group is recognized by a unique hydrophobic pocket, which includes Glu88, Leu91 and Leu92 from subunit 1 and Val193' from subunit 2. CONCLUSIONS: A large movement of domain 1 is induced by substrate binding, which results in the formation of the hydrophobic pocket for the gamma-isopropyl moiety of IPM. A glutamic acid in domain 1, Glu88, participates in the formation of the hydrophobic pocket. The C beta and C gamma atoms of Glu88 interact with the gamma-isopropyl moiety of IPM and are central to the recognition of substrate. The acidic tip of Glu88 is likely to interact with the nicotinamide mononucleotide (NMN) ribose of NAD+ in the ternary complex. This structure clearly explains the substrate specificity of IPMDH.
About this Structure
1A05 is a Single protein structure of sequence from Acidithiobacillus ferrooxidans with and as ligands. Active as 3-isopropylmalate dehydrogenase, with EC number 1.1.1.85 Full crystallographic information is available from OCA.
Reference
Structure of 3-isopropylmalate dehydrogenase in complex with 3-isopropylmalate at 2.0 A resolution: the role of Glu88 in the unique substrate-recognition mechanism., Imada K, Inagaki K, Matsunami H, Kawaguchi H, Tanaka H, Tanaka N, Namba K, Structure. 1998 Aug 15;6(8):971-82. PMID:9739088
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