1o92
From Proteopedia
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==Overview== | ==Overview== | ||
| - | Methionine adenosyltransferases (MATs) are a family of enzymes in charge, of synthesising S-adenosylmethionine (SAM), the most important methyl, donor present in living organisms. These enzymes use methionine and ATP as, reaction substrates, which react in a S(N)2 fashion where the sulphur atom, from methionine attacks C5' from ATP while triphosphate chain is cleaved., A MAT liver specific isoenzyme has been detected, which exists in two, distinct oligomeric forms, a dimer (MAT III) and a tetramer (MAT I). Our, previously reported crystal structure of MAT I complexed with an inhibitor, led to the identification of the methionine-binding site. We present here, the results obtained from the complex of MAT I with a competitive, inhibitor of methionine, (2S,4S)-amino-4,5-epoxypentanoic acid ... | + | Methionine adenosyltransferases (MATs) are a family of enzymes in charge, of synthesising S-adenosylmethionine (SAM), the most important methyl, donor present in living organisms. These enzymes use methionine and ATP as, reaction substrates, which react in a S(N)2 fashion where the sulphur atom, from methionine attacks C5' from ATP while triphosphate chain is cleaved., A MAT liver specific isoenzyme has been detected, which exists in two, distinct oligomeric forms, a dimer (MAT III) and a tetramer (MAT I). Our, previously reported crystal structure of MAT I complexed with an inhibitor, led to the identification of the methionine-binding site. We present here, the results obtained from the complex of MAT I with a competitive, inhibitor of methionine, (2S,4S)-amino-4,5-epoxypentanoic acid (AEP), which presents the same features at the methionine binding site reported, before. We have also analysed several complexes of this enzyme with, methionine and ATP and analogues of them, in order to characterise the, interaction that is produced between both substrates. The crystal, structures of the complexes reveal how the substrates recognise each other, at the active site of the enzyme, and suggest a putative binding site for, the product SAM. The residues involved in the interactions of substrates, and products with MAT have been identified, and the results agree with all, the previous data concerning mutagenesis experiments and crystallographic, work. Moreover, all the information provided from the analysis of the, complexes has allowed us to postulate a catalytic mechanism for this, family of enzymes. In particular, we propose a key role for Lys182 in the, correct positioning of the substrates, and Asp135(*), in stabilising the, sulphonium group formed in the product (SAM). |
==About this Structure== | ==About this Structure== | ||
| - | 1O92 is a | + | 1O92 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus] with PO4, MG, K, AMB and ADP as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Methionine_adenosyltransferase Methionine adenosyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.5.1.6 2.5.1.6] Structure known Active Site: ADP. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1O92 OCA]. |
==Reference== | ==Reference== | ||
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[[Category: transferase]] | [[Category: transferase]] | ||
| - | ''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 15:09:38 2007'' |
Revision as of 13:04, 5 November 2007
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METHIONINE ADENOSYLTRANSFERASE COMPLEXED WITH ADP AND A L-METHIONINE ANALOGOUS
Overview
Methionine adenosyltransferases (MATs) are a family of enzymes in charge, of synthesising S-adenosylmethionine (SAM), the most important methyl, donor present in living organisms. These enzymes use methionine and ATP as, reaction substrates, which react in a S(N)2 fashion where the sulphur atom, from methionine attacks C5' from ATP while triphosphate chain is cleaved., A MAT liver specific isoenzyme has been detected, which exists in two, distinct oligomeric forms, a dimer (MAT III) and a tetramer (MAT I). Our, previously reported crystal structure of MAT I complexed with an inhibitor, led to the identification of the methionine-binding site. We present here, the results obtained from the complex of MAT I with a competitive, inhibitor of methionine, (2S,4S)-amino-4,5-epoxypentanoic acid (AEP), which presents the same features at the methionine binding site reported, before. We have also analysed several complexes of this enzyme with, methionine and ATP and analogues of them, in order to characterise the, interaction that is produced between both substrates. The crystal, structures of the complexes reveal how the substrates recognise each other, at the active site of the enzyme, and suggest a putative binding site for, the product SAM. The residues involved in the interactions of substrates, and products with MAT have been identified, and the results agree with all, the previous data concerning mutagenesis experiments and crystallographic, work. Moreover, all the information provided from the analysis of the, complexes has allowed us to postulate a catalytic mechanism for this, family of enzymes. In particular, we propose a key role for Lys182 in the, correct positioning of the substrates, and Asp135(*), in stabilising the, sulphonium group formed in the product (SAM).
About this Structure
1O92 is a Single protein structure of sequence from Rattus norvegicus with PO4, MG, K, AMB and ADP as ligands. Active as Methionine adenosyltransferase, with EC number 2.5.1.6 Structure known Active Site: ADP. Full crystallographic information is available from OCA.
Reference
Crystal structures of methionine adenosyltransferase complexed with substrates and products reveal the methionine-ATP recognition and give insights into the catalytic mechanism., Gonzalez B, Pajares MA, Hermoso JA, Guillerm D, Guillerm G, Sanz-Aparicio J, J Mol Biol. 2003 Aug 8;331(2):407-16. PMID:12888348
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