1hwy
From Proteopedia
(New page: 200px<br /><applet load="1hwy" size="450" color="white" frame="true" align="right" spinBox="true" caption="1hwy, resolution 3.2Å" /> '''BOVINE GLUTAMATE DEHY...) |
|||
| Line 1: | Line 1: | ||
| - | [[Image:1hwy.gif|left|200px]]<br /><applet load="1hwy" size=" | + | [[Image:1hwy.gif|left|200px]]<br /><applet load="1hwy" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1hwy, resolution 3.2Å" /> | caption="1hwy, resolution 3.2Å" /> | ||
'''BOVINE GLUTAMATE DEHYDROGENASE COMPLEXED WITH NAD AND 2-OXOGLUTARATE'''<br /> | '''BOVINE GLUTAMATE DEHYDROGENASE COMPLEXED WITH NAD AND 2-OXOGLUTARATE'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Glutamate dehydrogenase is found in all organisms and catalyses the | + | Glutamate dehydrogenase is found in all organisms and catalyses the oxidative deamination of l-glutamate to 2-oxoglutarate. However, only animal GDH utilizes both NAD(H) or NADP(H) with comparable efficacy and exhibits a complex pattern of allosteric inhibition by a wide variety of small molecules. The major allosteric inhibitors are GTP and NADH and the two main allosteric activators are ADP and NAD(+). The structures presented here have refined and modified the previous structural model of allosteric regulation inferred from the original boGDH.NADH.GLU.GTP complex. The boGDH.NAD(+).alpha-KG complex structure clearly demonstrates that the second coenzyme-binding site lies directly under the "pivot helix" of the NAD(+) binding domain. In this complex, phosphates are observed to occupy the inhibitory GTP site and may be responsible for the previously observed structural stabilization by polyanions. The boGDH.NADPH.GLU.GTP complex shows the location of the additional phosphate on the active site coenzyme molecule and the GTP molecule bound to the GTP inhibitory site. As expected, since NADPH does not bind well to the second coenzyme site, no evidence of a bound molecule is observed at the second coenzyme site under the pivot helix. Therefore, these results suggest that the inhibitory GTP site is as previously identified. However, ADP, NAD(+), and NADH all bind under the pivot helix, but a second GTP molecule does not. Kinetic analysis of a hyperinsulinism/hyperammonemia mutant strongly suggests that ATP can inhibit the reaction by binding to the GTP site. Finally, the fact that NADH, NAD(+), and ADP all bind to the same site requires a re-analysis of the previous models for NADH inhibition. |
==About this Structure== | ==About this Structure== | ||
| - | 1HWY is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Bos_taurus Bos taurus] with PO4, AKG and NAD as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Glutamate_dehydrogenase_(NAD(P)(+)) Glutamate dehydrogenase (NAD(P)(+))], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.4.1.3 1.4.1.3] Full crystallographic information is available from [http:// | + | 1HWY is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Bos_taurus Bos taurus] with <scene name='pdbligand=PO4:'>PO4</scene>, <scene name='pdbligand=AKG:'>AKG</scene> and <scene name='pdbligand=NAD:'>NAD</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Glutamate_dehydrogenase_(NAD(P)(+)) Glutamate dehydrogenase (NAD(P)(+))], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.4.1.3 1.4.1.3] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1HWY OCA]. |
==Reference== | ==Reference== | ||
| Line 15: | Line 15: | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Fang, J.]] | [[Category: Fang, J.]] | ||
| - | [[Category: Peterson, P | + | [[Category: Peterson, P E.]] |
[[Category: Schmidt, T.]] | [[Category: Schmidt, T.]] | ||
| - | [[Category: Smith, T | + | [[Category: Smith, T J.]] |
| - | [[Category: Stanley, C | + | [[Category: Stanley, C A.]] |
[[Category: AKG]] | [[Category: AKG]] | ||
[[Category: NAD]] | [[Category: NAD]] | ||
| Line 26: | Line 26: | ||
[[Category: nad]] | [[Category: nad]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:05:37 2008'' |
Revision as of 11:05, 21 February 2008
|
BOVINE GLUTAMATE DEHYDROGENASE COMPLEXED WITH NAD AND 2-OXOGLUTARATE
Overview
Glutamate dehydrogenase is found in all organisms and catalyses the oxidative deamination of l-glutamate to 2-oxoglutarate. However, only animal GDH utilizes both NAD(H) or NADP(H) with comparable efficacy and exhibits a complex pattern of allosteric inhibition by a wide variety of small molecules. The major allosteric inhibitors are GTP and NADH and the two main allosteric activators are ADP and NAD(+). The structures presented here have refined and modified the previous structural model of allosteric regulation inferred from the original boGDH.NADH.GLU.GTP complex. The boGDH.NAD(+).alpha-KG complex structure clearly demonstrates that the second coenzyme-binding site lies directly under the "pivot helix" of the NAD(+) binding domain. In this complex, phosphates are observed to occupy the inhibitory GTP site and may be responsible for the previously observed structural stabilization by polyanions. The boGDH.NADPH.GLU.GTP complex shows the location of the additional phosphate on the active site coenzyme molecule and the GTP molecule bound to the GTP inhibitory site. As expected, since NADPH does not bind well to the second coenzyme site, no evidence of a bound molecule is observed at the second coenzyme site under the pivot helix. Therefore, these results suggest that the inhibitory GTP site is as previously identified. However, ADP, NAD(+), and NADH all bind under the pivot helix, but a second GTP molecule does not. Kinetic analysis of a hyperinsulinism/hyperammonemia mutant strongly suggests that ATP can inhibit the reaction by binding to the GTP site. Finally, the fact that NADH, NAD(+), and ADP all bind to the same site requires a re-analysis of the previous models for NADH inhibition.
About this Structure
1HWY is a Single protein structure of sequence from Bos taurus with , and as ligands. Active as Glutamate dehydrogenase (NAD(P)(+)), with EC number 1.4.1.3 Full crystallographic information is available from OCA.
Reference
Structures of bovine glutamate dehydrogenase complexes elucidate the mechanism of purine regulation., Smith TJ, Peterson PE, Schmidt T, Fang J, Stanley CA, J Mol Biol. 2001 Mar 23;307(2):707-20. PMID:11254391
Page seeded by OCA on Thu Feb 21 13:05:37 2008
