1jl0
From Proteopedia
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|PDB= 1jl0 |SIZE=350|CAPTION= <scene name='initialview01'>1jl0</scene>, resolution 1.50Å | |PDB= 1jl0 |SIZE=350|CAPTION= <scene name='initialview01'>1jl0</scene>, resolution 1.50Å | ||
|SITE= | |SITE= | ||
| - | |LIGAND= <scene name='pdbligand=PUT:1,4-DIAMINOBUTANE'>PUT</scene> | + | |LIGAND= <scene name='pdbligand=PUT:1,4-DIAMINOBUTANE'>PUT</scene>, <scene name='pdbligand=TRS:2-AMINO-2-HYDROXYMETHYL-PROPANE-1,3-DIOL'>TRS</scene> |
| - | |ACTIVITY= [http://en.wikipedia.org/wiki/Adenosylmethionine_decarboxylase Adenosylmethionine decarboxylase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.1.1.50 4.1.1.50] | + | |ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/Adenosylmethionine_decarboxylase Adenosylmethionine decarboxylase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.1.1.50 4.1.1.50] </span> |
|GENE= | |GENE= | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY=[[1jen|1JEN]] | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1jl0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1jl0 OCA], [http://www.ebi.ac.uk/pdbsum/1jl0 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1jl0 RCSB]</span> | ||
}} | }} | ||
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==Overview== | ==Overview== | ||
S-Adenosylmethionine decarboxylase (AdoMetDC) is synthesized as a proenzyme that cleaves itself in a putrescine-stimulated reaction via an N-->O acyl shift and beta-elimination to produce an active enzyme with a catalytically essential pyruvoyl residue at the new N-terminus. N-->O acyl shifts initiate the self-processing of other proteins such as inteins and amidohydrolases, but their mechanisms in such proteins are not well understood. We have solved the crystal structure of the H243A mutant of AdoMetDC to 1.5 A resolution. The mutant protein is trapped in the ester form, providing clear evidence for the structure of the ester intermediate in the processing of pyruvoyl enzymes. In addition, a putrescine molecule is bound in a charged region within the beta-sandwich, and cross-links the two beta-sheets through hydrogen bonds to several acidic residues and ordered water molecules. The high-resolution structure provides insight into the mechanism for the self-processing reaction and provides evidence for the mechanism for simulation of the self-processing reaction by putrescine. Studies of the effects of putrescine or 4-aminobutanol on the processing of mutant AdoMetDC proenzymes are consistent with a model in which a single activator molecule interacts with buried Asp174, Glu178, and Glu256, leading to an alteration in the position of Glu11, resulting in stimulation of self-processing. | S-Adenosylmethionine decarboxylase (AdoMetDC) is synthesized as a proenzyme that cleaves itself in a putrescine-stimulated reaction via an N-->O acyl shift and beta-elimination to produce an active enzyme with a catalytically essential pyruvoyl residue at the new N-terminus. N-->O acyl shifts initiate the self-processing of other proteins such as inteins and amidohydrolases, but their mechanisms in such proteins are not well understood. We have solved the crystal structure of the H243A mutant of AdoMetDC to 1.5 A resolution. The mutant protein is trapped in the ester form, providing clear evidence for the structure of the ester intermediate in the processing of pyruvoyl enzymes. In addition, a putrescine molecule is bound in a charged region within the beta-sandwich, and cross-links the two beta-sheets through hydrogen bonds to several acidic residues and ordered water molecules. The high-resolution structure provides insight into the mechanism for the self-processing reaction and provides evidence for the mechanism for simulation of the self-processing reaction by putrescine. Studies of the effects of putrescine or 4-aminobutanol on the processing of mutant AdoMetDC proenzymes are consistent with a model in which a single activator molecule interacts with buried Asp174, Glu178, and Glu256, leading to an alteration in the position of Glu11, resulting in stimulation of self-processing. | ||
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| - | ==Disease== | ||
| - | Known disease associated with this structure: Acromesomelic dysplasia, Maroteaux type OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=108961 108961]] | ||
==About this Structure== | ==About this Structure== | ||
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[[Category: Tolbert, W D.]] | [[Category: Tolbert, W D.]] | ||
[[Category: Xiong, H.]] | [[Category: Xiong, H.]] | ||
| - | [[Category: PUT]] | ||
| - | [[Category: TRS]] | ||
[[Category: allosteric enzyme]] | [[Category: allosteric enzyme]] | ||
[[Category: decarboxylase]] | [[Category: decarboxylase]] | ||
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[[Category: spermidine biosynthesis]] | [[Category: spermidine biosynthesis]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 21:35:11 2008'' |
Revision as of 18:35, 30 March 2008
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| , resolution 1.50Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , | ||||||
| Activity: | Adenosylmethionine decarboxylase, with EC number 4.1.1.50 | ||||||
| Related: | 1JEN
| ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Structure of a Human S-Adenosylmethionine Decarboxylase Self-processing Ester Intermediate and Mechanism of Putrescine Stimulation of Processing as Revealed by the H243A Mutant
Overview
S-Adenosylmethionine decarboxylase (AdoMetDC) is synthesized as a proenzyme that cleaves itself in a putrescine-stimulated reaction via an N-->O acyl shift and beta-elimination to produce an active enzyme with a catalytically essential pyruvoyl residue at the new N-terminus. N-->O acyl shifts initiate the self-processing of other proteins such as inteins and amidohydrolases, but their mechanisms in such proteins are not well understood. We have solved the crystal structure of the H243A mutant of AdoMetDC to 1.5 A resolution. The mutant protein is trapped in the ester form, providing clear evidence for the structure of the ester intermediate in the processing of pyruvoyl enzymes. In addition, a putrescine molecule is bound in a charged region within the beta-sandwich, and cross-links the two beta-sheets through hydrogen bonds to several acidic residues and ordered water molecules. The high-resolution structure provides insight into the mechanism for the self-processing reaction and provides evidence for the mechanism for simulation of the self-processing reaction by putrescine. Studies of the effects of putrescine or 4-aminobutanol on the processing of mutant AdoMetDC proenzymes are consistent with a model in which a single activator molecule interacts with buried Asp174, Glu178, and Glu256, leading to an alteration in the position of Glu11, resulting in stimulation of self-processing.
About this Structure
1JL0 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Structure of a human S-adenosylmethionine decarboxylase self-processing ester intermediate and mechanism of putrescine stimulation of processing as revealed by the H243A mutant., Ekstrom JL, Tolbert WD, Xiong H, Pegg AE, Ealick SE, Biochemistry. 2001 Aug 14;40(32):9495-504. PMID:11583148
Page seeded by OCA on Sun Mar 30 21:35:11 2008
Categories: Adenosylmethionine decarboxylase | Homo sapiens | Single protein | Ealick, S E. | Ekstrom, J L. | Pegg, A E. | Tolbert, W D. | Xiong, H. | Allosteric enzyme | Decarboxylase | Ester intermediate | Hydroxyalanine | Lyase | Pyruvate | Pyruvoyl | S-adenosylmethionine | Sandwich | Spermidine biosynthesis
