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| | {{STRUCTURE_1qm4| PDB=1qm4 | SCENE= }} | | {{STRUCTURE_1qm4| PDB=1qm4 | SCENE= }} |
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| - | '''METHIONINE ADENOSYLTRANSFERASE COMPLEXED WITH A L-METHIONINE ANALOGOUS'''
| + | ===METHIONINE ADENOSYLTRANSFERASE COMPLEXED WITH A L-METHIONINE ANALOGOUS=== |
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| - | ==Overview==
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| - | Most of the transmethylation reactions use the same methyl donor, S-adenosylmethionine (SAM), that is synthesised from methionine and ATP by methionine adenosyltransferase (MAT). In mammals, two MAT enzymes have been detected, one ubiquitous and another liver specific. The liver enzyme exists in two oligomeric forms, a tetramer (MAT I) and a dimer (MAT III), MAT I being the one that shows a higher level of affinity for methionine but a lower SAM synthesis capacity. We have solved the crystal structure of rat liver MAT I at 2.7 A resolution, complexed with a methionine analogue: l-2-amino-4-methoxy-cis-but-3-enoic acid (l-cisAMB). The enzyme consists of four identical subunits arranged in two tight dimers that are related by crystallographic 2-fold symmetry. The crystal structure shows the positions of the relevant cysteine residues in the chain, and that Cys35 and Cys61 are perfectly oriented for forming a disulphide link. This result leads us to propose a hypothesis to explain the control of MAT I/III exchange and hence, the effects observed on activity. We have identified the methionine-binding site into the active-site cavity, for the first time. The l-cisAMB inhibitor is stacked against Phe251 aromatic ring in a rather planar conformation, and its carboxylate group coordinates a Mg(2+), which, in turn, is linked to Asp180. The essential role of the involved residues in MAT activity has been confirmed by site-directed mutagenesis. Phe251 is exposed to solvent and is located in the beginning of the flexible loop Phe251-Ala260 that is connecting the N-terminal domain to the central domain. We postulate that a conformational change may take place during the enzymatic reaction and this is possibly the reason of the unusual two-step mechanism involving tripolyphosphate hydrolysis. Other important mechanistic implications are discussed on the light of the results. Moreover, the critical role that certain residues identified in this study may have in methionine recognition opens further possibilities for rational drug design.
| + | The line below this paragraph, {{ABSTRACT_PUBMED_10873471}}, adds the Publication Abstract to the page |
| | + | (as it appears on PubMed at http://www.pubmed.gov), where 10873471 is the PubMed ID number. |
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| | + | {{ABSTRACT_PUBMED_10873471}} |
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| | ==About this Structure== | | ==About this Structure== |
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| | [[Category: Adenosyltransferase]] | | [[Category: Adenosyltransferase]] |
| | [[Category: Methionine binding]] | | [[Category: Methionine binding]] |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 06:26:20 2008'' | + | |
| | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 29 08:26:24 2008'' |
Revision as of 05:26, 29 July 2008
Template:STRUCTURE 1qm4
METHIONINE ADENOSYLTRANSFERASE COMPLEXED WITH A L-METHIONINE ANALOGOUS
Template:ABSTRACT PUBMED 10873471
About this Structure
1QM4 is a Single protein structure of sequence from Rattus norvegicus. Full crystallographic information is available from OCA.
Reference
The crystal structure of tetrameric methionine adenosyltransferase from rat liver reveals the methionine-binding site., Gonzalez B, Pajares MA, Hermoso JA, Alvarez L, Garrido F, Sufrin JR, Sanz-Aparicio J, J Mol Biol. 2000 Jul 7;300(2):363-75. PMID:10873471
Page seeded by OCA on Tue Jul 29 08:26:24 2008
