1eji
From Proteopedia
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==Overview== | ==Overview== | ||
| - | Serine hydroxymethyltransferase (SHMT) is a pyridoxal phosphate-dependent, enzyme that catalyzes the reversible conversion of serine and, tetrahydrofolate to glycine and methylenetetrahydrofolate. This reaction, generates single carbon units for purine, thymidine, and methionine, biosynthesis. The enzyme is a homotetramer comprising two obligate dimers, and four pyridoxal phosphate-bound active sites. The mammalian enzyme is, present in cells in both catalytically active and inactive forms. The, inactive form is a ternary complex that results from the binding of, glycine and 5-formyltetrahydrofolate polyglutamate, a slow tight-binding, inhibitor. The crystal structure of a close analogue of the inactive form, of murine cytoplasmic SHMT (cSHMT), lacking only the polyglutamate tail of, the ... | + | Serine hydroxymethyltransferase (SHMT) is a pyridoxal phosphate-dependent, enzyme that catalyzes the reversible conversion of serine and, tetrahydrofolate to glycine and methylenetetrahydrofolate. This reaction, generates single carbon units for purine, thymidine, and methionine, biosynthesis. The enzyme is a homotetramer comprising two obligate dimers, and four pyridoxal phosphate-bound active sites. The mammalian enzyme is, present in cells in both catalytically active and inactive forms. The, inactive form is a ternary complex that results from the binding of, glycine and 5-formyltetrahydrofolate polyglutamate, a slow tight-binding, inhibitor. The crystal structure of a close analogue of the inactive form, of murine cytoplasmic SHMT (cSHMT), lacking only the polyglutamate tail of, the inhibitor, has been determined to 2.9 A resolution. This first, structure of a ligand-bound mammalian SHMT allows identification of amino, acid residues involved in substrate binding and catalysis. It also reveals, that the two obligate dimers making up a tetramer are not equivalent; one, can be described as "tight-binding" and the other as "loose-binding" for, folate. Both active sites of the tight-binding dimer are occupied by, 5-formyltetrahydrofolate (5-formylTHF), whose N5-formyl carbon is within 4, A of the glycine alpha-carbon of the glycine-pyridoxal phosphate complex;, the complex appears to be primarily in its quinonoid form. In the, loose-binding dimer, 5-formylTHF is present in only one of the active, sites, and its N5-formyl carbon is 5 A from the glycine alpha-carbon. The, pyridoxal phosphates appear to be primarily present as geminal diamine, complexes, with bonds to both glycine and the active site lysine. This, structure suggests that only two of the four catalytic sites on SHMT are, catalytically competent and that the cSHMT-glycine-5-formylTHF ternary, complex is an intermediate state analogue of the catalytic complex, associated with serine and glycine interconversion. |
==About this Structure== | ==About this Structure== | ||
| - | 1EJI is a | + | 1EJI is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus] with PLG and THF as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Glycine_hydroxymethyltransferase Glycine hydroxymethyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.1.2.1 2.1.2.1] Structure known Active Sites: I, II, III and IV. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1EJI OCA]. |
==Reference== | ==Reference== | ||
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[[Category: tetrahydrofolate]] | [[Category: tetrahydrofolate]] | ||
| - | ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 5 12:31:43 2007'' |
Revision as of 10:26, 5 November 2007
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RECOMBINANT SERINE HYDROXYMETHYLTRANSFERASE (MOUSE)
Overview
Serine hydroxymethyltransferase (SHMT) is a pyridoxal phosphate-dependent, enzyme that catalyzes the reversible conversion of serine and, tetrahydrofolate to glycine and methylenetetrahydrofolate. This reaction, generates single carbon units for purine, thymidine, and methionine, biosynthesis. The enzyme is a homotetramer comprising two obligate dimers, and four pyridoxal phosphate-bound active sites. The mammalian enzyme is, present in cells in both catalytically active and inactive forms. The, inactive form is a ternary complex that results from the binding of, glycine and 5-formyltetrahydrofolate polyglutamate, a slow tight-binding, inhibitor. The crystal structure of a close analogue of the inactive form, of murine cytoplasmic SHMT (cSHMT), lacking only the polyglutamate tail of, the inhibitor, has been determined to 2.9 A resolution. This first, structure of a ligand-bound mammalian SHMT allows identification of amino, acid residues involved in substrate binding and catalysis. It also reveals, that the two obligate dimers making up a tetramer are not equivalent; one, can be described as "tight-binding" and the other as "loose-binding" for, folate. Both active sites of the tight-binding dimer are occupied by, 5-formyltetrahydrofolate (5-formylTHF), whose N5-formyl carbon is within 4, A of the glycine alpha-carbon of the glycine-pyridoxal phosphate complex;, the complex appears to be primarily in its quinonoid form. In the, loose-binding dimer, 5-formylTHF is present in only one of the active, sites, and its N5-formyl carbon is 5 A from the glycine alpha-carbon. The, pyridoxal phosphates appear to be primarily present as geminal diamine, complexes, with bonds to both glycine and the active site lysine. This, structure suggests that only two of the four catalytic sites on SHMT are, catalytically competent and that the cSHMT-glycine-5-formylTHF ternary, complex is an intermediate state analogue of the catalytic complex, associated with serine and glycine interconversion.
About this Structure
1EJI is a Single protein structure of sequence from Mus musculus with PLG and THF as ligands. Active as Glycine hydroxymethyltransferase, with EC number 2.1.2.1 Structure known Active Sites: I, II, III and IV. Full crystallographic information is available from OCA.
Reference
Structure of a murine cytoplasmic serine hydroxymethyltransferase quinonoid ternary complex: evidence for asymmetric obligate dimers., Szebenyi DM, Liu X, Kriksunov IA, Stover PJ, Thiel DJ, Biochemistry. 2000 Nov 7;39(44):13313-23. PMID:11063567
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