1msv: Difference between revisions
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[[Image:1msv.gif|left|200px]] | [[Image:1msv.gif|left|200px]] | ||
'''The S68A S-adenosylmethionine decarboxylase proenzyme processing mutant.''' | {{Structure | ||
|PDB= 1msv |SIZE=350|CAPTION= <scene name='initialview01'>1msv</scene>, resolution 1.75Å | |||
|SITE= | |||
|LIGAND= <scene name='pdbligand=PUT:1,4-DIAMINOBUTANE'>PUT</scene> and <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] | |||
|GENE= | |||
}} | |||
'''The S68A S-adenosylmethionine decarboxylase proenzyme processing mutant.''' | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
1MSV is a [ | 1MSV is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1MSV OCA]. | ||
==Reference== | ==Reference== | ||
Mechanism of human S-adenosylmethionine decarboxylase proenzyme processing as revealed by the structure of the S68A mutant., Tolbert WD, Zhang Y, Cottet SE, Bennett EM, Ekstrom JL, Pegg AE, Ealick SE, Biochemistry. 2003 Mar 4;42(8):2386-95. PMID:[http:// | Mechanism of human S-adenosylmethionine decarboxylase proenzyme processing as revealed by the structure of the S68A mutant., Tolbert WD, Zhang Y, Cottet SE, Bennett EM, Ekstrom JL, Pegg AE, Ealick SE, Biochemistry. 2003 Mar 4;42(8):2386-95. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/12600205 12600205] | ||
[[Category: Adenosylmethionine decarboxylase]] | [[Category: Adenosylmethionine decarboxylase]] | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
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[[Category: spermidine biosynthesis]] | [[Category: spermidine biosynthesis]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 12:47:44 2008'' | ||
Revision as of 13:47, 20 March 2008
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| , resolution 1.75Å | |||||||
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| Ligands: | and | ||||||
| Activity: | Adenosylmethionine decarboxylase, with EC number 4.1.1.50 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
The S68A S-adenosylmethionine decarboxylase proenzyme processing mutant.
OverviewOverview
S-Adenosylmethionine decarboxylase (AdoMetDC) is a pyruvoyl-dependent enzyme that catalyzes the formation of the aminopropyl group donor in the biosynthesis of the polyamines spermidine and spermine. The enzyme is synthesized as a protein precursor and is activated by an autocatalytic serinolysis reaction that creates the pyruvoyl group. The autoprocessing reaction proceeds via an N --> O acyl rearrangement, generating first an oxyoxazolidine anion intermediate followed by an ester intermediate. A similar strategy is utilized in self-catalyzed protein splicing reactions and in autoproteolytic activation of protein precursors. Mutation of Ser68 to alanine in human AdoMetDC prevents processing by removing the serine side chain necessary for nucleophilic attack at the adjacent carbonyl carbon atom. We have determined the X-ray structure of the S68A mutant and have constructed models of the proenzyme and the oxyoxazolidine intermediate. Formation of the oxyoxazolidine intermediate is promoted by a hydrogen bond from Cys82 and stabilized by a hydrogen bond from Ser229. These observations are consistent with mutagenesis studies, which show that the C82S and C82A mutants process slowly and that the S229A mutant does not process at all. Donation of a proton by His243 to the nitrogen atom of the oxyoxazolidine ring converts the oxyoxazolidine anion to the ester intermediate. The absence of a base to activate the hydroxyl group of Ser68 suggests that strain may play a role in the cleavage reaction. Comparison of AdoMetDC with other self-processing proteins shows no common structural features. Comparison to histidine decarboxylase and aspartate decarboxylase shows that these pyruvoyl-dependent enzymes evolved different catalytic strategies for forming the same cofactor.
DiseaseDisease
Known disease associated with this structure: Acromesomelic dysplasia, Maroteaux type OMIM:[108961]
About this StructureAbout this Structure
1MSV is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
Mechanism of human S-adenosylmethionine decarboxylase proenzyme processing as revealed by the structure of the S68A mutant., Tolbert WD, Zhang Y, Cottet SE, Bennett EM, Ekstrom JL, Pegg AE, Ealick SE, Biochemistry. 2003 Mar 4;42(8):2386-95. PMID:12600205
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