1l7p
From Proteopedia
(New page: 200px<br /><applet load="1l7p" size="450" color="white" frame="true" align="right" spinBox="true" caption="1l7p, resolution 1.9Å" /> '''SUBSTRATE BOUND PHOSP...) |
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| - | [[Image:1l7p.gif|left|200px]]<br /><applet load="1l7p" size=" | + | [[Image:1l7p.gif|left|200px]]<br /><applet load="1l7p" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1l7p, resolution 1.9Å" /> | caption="1l7p, resolution 1.9Å" /> | ||
'''SUBSTRATE BOUND PHOSPHOSERINE PHOSPHATASE COMPLEX STRUCTURE'''<br /> | '''SUBSTRATE BOUND PHOSPHOSERINE PHOSPHATASE COMPLEX STRUCTURE'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Phosphoserine phosphatase (PSP) is a member of a large class of enzymes | + | Phosphoserine phosphatase (PSP) is a member of a large class of enzymes that catalyze phosphoester hydrolysis using a phosphoaspartate-enzyme intermediate. PSP is a likely regulator of the steady-state d-serine level in the brain, which is a critical co-agonist of the N-methyl-d-aspartate type of glutamate receptors. Here, we present high-resolution (1.5-1.9 A) structures of PSP from Methanococcus jannaschii, which define the open state prior to substrate binding, the complex with phosphoserine substrate bound (with a D to N mutation in the active site), and the complex with AlF3, a transition-state analog for the phospho-transfer steps in the reaction. These structures, together with those described for the BeF3- complex (mimicking the phospho-enzyme) and the enzyme with phosphate product in the active site, provide a detailed structural picture of the full reaction cycle. The structure of the apo state indicates partial unfolding of the enzyme to allow substrate binding, with refolding in the presence of substrate to provide specificity. Interdomain and active-site conformational changes are identified. The structure with the transition state analog bound indicates a "tight" intermediate. A striking structure homology, with significant sequence conservation, among PSP, P-type ATPases and response regulators suggests that the knowledge of the PSP reaction mechanism from the structures determined will provide insights into the reaction mechanisms of the other enzymes in this family. |
==About this Structure== | ==About this Structure== | ||
| - | 1L7P is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Methanocaldococcus_jannaschii Methanocaldococcus jannaschii] with PO4 and SEP as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Phosphoserine_phosphatase Phosphoserine phosphatase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.3.3 3.1.3.3] Full crystallographic information is available from [http:// | + | 1L7P is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Methanocaldococcus_jannaschii Methanocaldococcus jannaschii] with <scene name='pdbligand=PO4:'>PO4</scene> and <scene name='pdbligand=SEP:'>SEP</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Phosphoserine_phosphatase Phosphoserine phosphatase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.3.3 3.1.3.3] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1L7P OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Phosphoserine phosphatase]] | [[Category: Phosphoserine phosphatase]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: BSGC, Berkeley | + | [[Category: BSGC, Berkeley Structural Genomics Center.]] |
| - | [[Category: Cho, H | + | [[Category: Cho, H S.]] |
| - | [[Category: Grigoriev, I | + | [[Category: Grigoriev, I V.]] |
[[Category: Jancarik, J.]] | [[Category: Jancarik, J.]] | ||
[[Category: Kim, R.]] | [[Category: Kim, R.]] | ||
| - | [[Category: Kim, S | + | [[Category: Kim, S H.]] |
| - | [[Category: Nguyen, H | + | [[Category: Nguyen, H H.]] |
[[Category: Wang, W.]] | [[Category: Wang, W.]] | ||
| - | [[Category: Wemmer, D | + | [[Category: Wemmer, D E.]] |
[[Category: Yokota, H.]] | [[Category: Yokota, H.]] | ||
[[Category: PO4]] | [[Category: PO4]] | ||
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[[Category: structural genomics]] | [[Category: structural genomics]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:42:17 2008'' |
Revision as of 11:42, 21 February 2008
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SUBSTRATE BOUND PHOSPHOSERINE PHOSPHATASE COMPLEX STRUCTURE
Overview
Phosphoserine phosphatase (PSP) is a member of a large class of enzymes that catalyze phosphoester hydrolysis using a phosphoaspartate-enzyme intermediate. PSP is a likely regulator of the steady-state d-serine level in the brain, which is a critical co-agonist of the N-methyl-d-aspartate type of glutamate receptors. Here, we present high-resolution (1.5-1.9 A) structures of PSP from Methanococcus jannaschii, which define the open state prior to substrate binding, the complex with phosphoserine substrate bound (with a D to N mutation in the active site), and the complex with AlF3, a transition-state analog for the phospho-transfer steps in the reaction. These structures, together with those described for the BeF3- complex (mimicking the phospho-enzyme) and the enzyme with phosphate product in the active site, provide a detailed structural picture of the full reaction cycle. The structure of the apo state indicates partial unfolding of the enzyme to allow substrate binding, with refolding in the presence of substrate to provide specificity. Interdomain and active-site conformational changes are identified. The structure with the transition state analog bound indicates a "tight" intermediate. A striking structure homology, with significant sequence conservation, among PSP, P-type ATPases and response regulators suggests that the knowledge of the PSP reaction mechanism from the structures determined will provide insights into the reaction mechanisms of the other enzymes in this family.
About this Structure
1L7P is a Single protein structure of sequence from Methanocaldococcus jannaschii with and as ligands. Active as Phosphoserine phosphatase, with EC number 3.1.3.3 Full crystallographic information is available from OCA.
Reference
Structural characterization of the reaction pathway in phosphoserine phosphatase: crystallographic "snapshots" of intermediate states., Wang W, Cho HS, Kim R, Jancarik J, Yokota H, Nguyen HH, Grigoriev IV, Wemmer DE, Kim SH, J Mol Biol. 2002 May 31;319(2):421-31. PMID:12051918
Page seeded by OCA on Thu Feb 21 13:42:17 2008
Categories: Methanocaldococcus jannaschii | Phosphoserine phosphatase | Single protein | BSGC, Berkeley Structural Genomics Center. | Cho, H S. | Grigoriev, I V. | Jancarik, J. | Kim, R. | Kim, S H. | Nguyen, H H. | Wang, W. | Wemmer, D E. | Yokota, H. | PO4 | SEP | Berkeley structural genomics center | Beta-hairpin | Bsgc structure funded by nih | Four-helix bundle | Protein structure initiative | Psi | Rossmann fold | Structural genomics
