Sandbox Reserved 345: Difference between revisions

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OCA, Kadagn Klepsch, Douglas Streifel

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 =S-Adenosylmethionine decarboxylase=
-S-Adenosylmethionine decarboxylase (AdoMetDC) is a key enzyme in the polyamine biosynthetic pathway, forming the amine decarboxylated S-adenosylmethionine <ref name="primary">PMID: 11583147</ref><ref name="two">PMID: 9353291</ref> It also aids in the synthesis of spermine and spermidine <ref name="primary"/><ref name="three">PMID: 11583148</ref><ref name="four">PMID: 12600205</ref>. Spermine and spermidine are polyamines that are essential growth factors and critical in cell differentiation <ref name="four"/><ref name="five">PMID: 19527050</ref>. Their levels within cells are regulated by the amount of AdoMetDC available ref name="four"/>. Thus, AdoMetDC is tightly regulated in mammalian cells <ref name="primary"/>.
+{{STRUCTURE_1i7c|PDB=1i7c|SCENE=}}
-{{STRUCTURE_3cs9|PDB=3cs9|SCENE=Sandbox_Reserved_345/Begining/1}}
+S-Adenosylmethionine decarboxylase (AdoMetDC) is a key enzyme in the polyamine biosynthetic pathway, forming the amine decarboxylated S-adenosylmethionine <ref name="primary">PMID: 11583147</ref><ref name="two">PMID: 9353291</ref> It also aids in the synthesis of spermine and spermidine <ref name="primary"/><ref name="three">PMID: 11583148</ref><ref name="four">PMID: 12600205</ref>. Spermine and spermidine are polyamines that are essential growth factors and critical in cell differentiation <ref name="four"/><ref name="five">PMID: 19527050</ref>. Their levels within cells are regulated by the amount of AdoMetDC available <ref name="four"/>. Thus, AdoMetDC is tightly regulated in mammalian cells <ref name="primary"/>.
 ==Structure and Function==
-S-Adenosylmethionine decarboxylase is a (αβ)2 dimer, forming a four-layer αββα sandwich <ref name="primary"/>.  The αβ monomers both have the same structure <ref name="primary"/>.  The β chain consists of the residues 1-67 while the α chain contains the residues 68-329 <ref name="four"/>. Each β sheet contains eight anti-parallel β strands <ref name="primary"/>.  AdoMetDC has a very unique fold compared to other large β-sandwich structures as well as other pyruvoyl-dependent amino acid decarboxylases <ref name="primary"/>. The two β sheets are connected by only one covalent bond which allows them a large amount of flexibility to behave as independently folded domains that move with respect to each other <ref name="primary"/>. The α and β subunits are formed by an internal cleavage reaction <ref name="primary"/>.
+S-Adenosylmethionine decarboxylase is a (αβ)2 <scene name='Sandbox_Reserved_345/Dimers/1'>dimer</scene> , forming a four-layer <scene name='Sandbox_Reserved_345/Alpha-beta/1'>αββα sandwich</scene>, <ref name="primary"/>.  The αβ monomers both have the same structure <ref name="primary"/>.  The β chain consists of the residues 1-67 while the α chain contains the residues 68-329 <ref name="four"/>. Each β sheet contains eight anti-parallel β strands <ref name="primary"/>.  AdoMetDC has a very unique fold compared to other large β-sandwich structures as well as other pyruvoyl-dependent amino acid decarboxylases <ref name="primary"/>. The two β sheets are connected by only one covalent bond which allows them a large amount of flexibility to behave as independently folded domains that move with respect to each other <ref name="primary"/>. The α and β subunits are formed by an internal cleavage reaction <ref name="primary"/>.
-AdoMetDC belongs to a small class of decarboxylating enzymes that use as a prosthetic group a covalently bound pyruvate <ref name="primary"/><ref name="two"/>. The same cleavage reaction that forms the α and β subunits also converts a serine (Ser68) residue into the pyruvate <ref name="two"/><ref name="three"/><ref name="six">PMID: 10029540</ref>. This self processing reaction occurs via a N to O acyl rearrangement <ref name="three"/><ref name="four"/>. The pyruvoyl group is bound to the N-terminal of an α subunit <ref name="four"/><ref name="five"/>.
+AdoMetDC belongs to a small class of decarboxylating enzymes that use as a prosthetic group a covalently bound <scene name='Sandbox_Reserved_345/Ligand/1'>pyruvate</scene> <ref name="primary"/><ref name="two"/>. The same cleavage reaction that forms the α and β subunits also converts a serine (Ser68) residue into the pyruvate <ref name="two"/><ref name="three"/><ref name="six">PMID: 10029540</ref>. This self processing reaction occurs via a N to O acyl rearrangement <ref name="three"/><ref name="four"/>. The pyruvoyl group is bound to the N-terminal of an α subunit <ref name="four"/><ref name="five"/>.
 Decarboxylation of S-adenosylmethionine (AdoMet) to S-adenosyl-5’-(3-methylthiopropylamine) (dcAdoMet) is catalyzed using AdoMetDC <ref name="two"/>. Spermidine is the receptor of the aminopropyl group from dcAdoMet forming spermine or spermidine <ref name="five"/>. This is an early step in the pathway of polyamine biosynthesis of dcAdoMet, which commits it completely to this fate <ref name="five"/>.
 ==Mechanism:==
 Binding of AdoMet to its enzyme AdoMetDC is the first step and binding occurs through the pyruvate prosthetic group, reacting to give a Schiff base <ref name="six"/>. The pyruvate then acts as an election sink, helping to break the carbon to carboxylic acid bond (C-COO-) resulting in a carbon dioxide (CO2) being eliminated <ref name="six"/>. Protonation occurs at the R carbon of the product resulting in the release of dcAdoMet <ref name="six"/>. This protonation also regenerates the pyruvate cofactor so that it is available and ready for another reaction <ref name="six"/>.
 ==References==
-<refernces/>
+<references/>
-. Tolbert WD, Ekstrom JL, Mathews II, Secrist JA, Kapoor P, Pegg AE, Ealick SE. The structural basis for substrate specificity and inhibition of human S-Adenosylmethionine decarboxylase. Biochem. 2001 Jun 21;40:9484-94.
-.Xiong H, Stanley BA, Tekwani BL, Pegg AE. Processing of mammalian and plant S-Adenosylmethionine decarboxylase proenzymes. J Biological Chem. 1997 Mar 11;272(45):28342-48.
-.Ekstrom JL, Tolbert WD, Xiong H, Pegg AE, Ealick SE. Structure of a human S-Adenosylmethionine decarboxylase self-processing ester intermediate and mechanism of putrescine stimulation of processing as revealed by the H243A mutant. Biochem. 2001Jun 5;40(32):9495-504.
-.Tolbert WD, Zhang Y, Cottet SE, Bennett EM, Ekstrom JL, Pegg AE, Ealick SE. Mechanism of human S-Adenosylmethionine decarboxylase proenzyme processing as revealed by the structure of the S68A mutant. Biochem. 2003 Feb 7;42(8):2386-95.
-.Bale S, Brooks W, Hans JW, Mahesan AM, Guida WC, Ealick SE. Role of the sulfonium center in determining the ligand specificity of human S-Adenosylmethionine decarboxylase. Biochem. 2009 Jun 15;48(27):6423-30.
-.Xiong H, Stanley BA, Pegg AE. Role of cysteine-82 in the catalytic mechanism of human S-Adenosylmethionine. Biochem. 1999 Feb 4;38(8):2462-70.