1mdr
From Proteopedia
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| - | [[Image:1mdr.gif|left|200px]] | + | [[Image:1mdr.gif|left|200px]] |
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| - | '''THE ROLE OF LYSINE 166 IN THE MECHANISM OF MANDELATE RACEMASE FROM PSEUDOMONAS PUTIDA: MECHANISTIC AND CRYSTALLOGRAPHIC EVIDENCE FOR STEREOSPECIFIC ALKYLATION BY (R)-ALPHA-PHENYLGLYCIDATE''' | + | {{Structure |
| + | |PDB= 1mdr |SIZE=350|CAPTION= <scene name='initialview01'>1mdr</scene>, resolution 2.1Å | ||
| + | |SITE= | ||
| + | |LIGAND= <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene> and <scene name='pdbligand=APG:ATROLACTIC ACID (2-PHENYL-LACTIC ACID)'>APG</scene> | ||
| + | |ACTIVITY= [http://en.wikipedia.org/wiki/Mandelate_racemase Mandelate racemase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=5.1.2.2 5.1.2.2] | ||
| + | |GENE= | ||
| + | }} | ||
| + | |||
| + | '''THE ROLE OF LYSINE 166 IN THE MECHANISM OF MANDELATE RACEMASE FROM PSEUDOMONAS PUTIDA: MECHANISTIC AND CRYSTALLOGRAPHIC EVIDENCE FOR STEREOSPECIFIC ALKYLATION BY (R)-ALPHA-PHENYLGLYCIDATE''' | ||
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==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1MDR is a [ | + | 1MDR is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Pseudomonas_putida Pseudomonas putida]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1MDR OCA]. |
==Reference== | ==Reference== | ||
| - | The role of lysine 166 in the mechanism of mandelate racemase from Pseudomonas putida: mechanistic and crystallographic evidence for stereospecific alkylation by (R)-alpha-phenylglycidate., Landro JA, Gerlt JA, Kozarich JW, Koo CW, Shah VJ, Kenyon GL, Neidhart DJ, Fujita S, Petsko GA, Biochemistry. 1994 Jan 25;33(3):635-43. PMID:[http:// | + | The role of lysine 166 in the mechanism of mandelate racemase from Pseudomonas putida: mechanistic and crystallographic evidence for stereospecific alkylation by (R)-alpha-phenylglycidate., Landro JA, Gerlt JA, Kozarich JW, Koo CW, Shah VJ, Kenyon GL, Neidhart DJ, Fujita S, Petsko GA, Biochemistry. 1994 Jan 25;33(3):635-43. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/8292591 8292591] |
[[Category: Mandelate racemase]] | [[Category: Mandelate racemase]] | ||
[[Category: Pseudomonas putida]] | [[Category: Pseudomonas putida]] | ||
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[[Category: racemase]] | [[Category: racemase]] | ||
| - | ''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 12:42:16 2008'' |
Revision as of 10:42, 20 March 2008
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| , resolution 2.1Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | and | ||||||
| Activity: | Mandelate racemase, with EC number 5.1.2.2 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
THE ROLE OF LYSINE 166 IN THE MECHANISM OF MANDELATE RACEMASE FROM PSEUDOMONAS PUTIDA: MECHANISTIC AND CRYSTALLOGRAPHIC EVIDENCE FOR STEREOSPECIFIC ALKYLATION BY (R)-ALPHA-PHENYLGLYCIDATE
Overview
The mechanism of irreversible inactivation of mandelate racemase (MR) from Pseudomonas putida by alpha-phenylglycidate (alpha PGA) has been investigated stereochemically and crystallographically. The (R) and (S) enantiomers of alpha PGA were synthesized in high enantiomeric excess (81% ee and 83% ee, respectively) using Sharpless epoxidation chemistry. (R)-alpha PGA was determined to be a stereospecific and stoichiometric irreversible inactivator of MR. (S)-alpha PGA does not inactivate MR and appears to bind noncovalently to the active site of MR with less affinity than that of (R)-alpha PGA. The X-ray crystal structure (2.0-A resolution) of MR inactivated by (R)-alpha PGA revealed the presence of a covalent adduct formed by nucleophilic attack of the epsilon-amino group of Lys 166 on the distal carbon on the epoxide ring of (R)-alpha PGA. The proximity of the alpha-proton of (S)-mandelate to Lys 166 [configurationally equivalent to (R)-alpha PGA] was corroborated by the crystal structure (2.1-A resolution) of MR complexed with the substrate analog/competitive inhibitor, (S)-atrolactate [(S)-alpha-methylmandelate]. These results support the proposal that Lys 166 is the polyvalent acid/base responsible for proton transfers on the (S) face of mandelate. In addition, the high-resolution structures also provide insight into the probable interactions of mandelate with the essential Mg2+ and functional groups in the active site.
About this Structure
1MDR is a Single protein structure of sequence from Pseudomonas putida. Full crystallographic information is available from OCA.
Reference
The role of lysine 166 in the mechanism of mandelate racemase from Pseudomonas putida: mechanistic and crystallographic evidence for stereospecific alkylation by (R)-alpha-phenylglycidate., Landro JA, Gerlt JA, Kozarich JW, Koo CW, Shah VJ, Kenyon GL, Neidhart DJ, Fujita S, Petsko GA, Biochemistry. 1994 Jan 25;33(3):635-43. PMID:8292591
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