1rp7
From Proteopedia
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'''E. COLI PYRUVATE DEHYDROGENASE INHIBITOR COMPLEX''' | '''E. COLI PYRUVATE DEHYDROGENASE INHIBITOR COMPLEX''' | ||
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Structural determinants of enzyme binding affinity: the E1 component of pyruvate dehydrogenase from Escherichia coli in complex with the inhibitor thiamin thiazolone diphosphate., Arjunan P, Chandrasekhar K, Sax M, Brunskill A, Nemeria N, Jordan F, Furey W, Biochemistry. 2004 Mar 9;43(9):2405-11. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/14992577 14992577] | Structural determinants of enzyme binding affinity: the E1 component of pyruvate dehydrogenase from Escherichia coli in complex with the inhibitor thiamin thiazolone diphosphate., Arjunan P, Chandrasekhar K, Sax M, Brunskill A, Nemeria N, Jordan F, Furey W, Biochemistry. 2004 Mar 9;43(9):2405-11. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/14992577 14992577] | ||
[[Category: Escherichia coli, and escherichia coli o157:h7]] | [[Category: Escherichia coli, and escherichia coli o157:h7]] | ||
| - | [[Category: Pyruvate dehydrogenase (acetyl-transferring)]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Arjunan, P.]] | [[Category: Arjunan, P.]] | ||
[[Category: Chandrasekhar, K.]] | [[Category: Chandrasekhar, K.]] | ||
[[Category: Furey, W.]] | [[Category: Furey, W.]] | ||
| - | [[Category: | + | [[Category: Pyruvate dehydrogenase]] |
| - | [[Category: | + | [[Category: Thdp]] |
| - | [[Category: | + | [[Category: Thiamin-thiazolone diphosphate]] |
| - | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 07:44:55 2008'' | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | |
Revision as of 04:44, 3 May 2008
E. COLI PYRUVATE DEHYDROGENASE INHIBITOR COMPLEX
Overview
Thiamin thiazolone diphosphate (ThTDP), a potent inhibitor of the E1 component from the Escherichia coli pyruvate dehydrogenase multienzyme complex (PDHc), binds to the enzyme with greater affinity than does the cofactor thiamin diphosphate (ThDP). To identify what determines this difference, the crystal structure of the apo PDHc E1 component complex with ThTDP and Mg(2+) has been determined at 2.1 A and compared to the known structure of the native holoenzyme, PDHc E1-ThDP-Mg(2+) complex. When ThTDP replaces ThDP, reorganization occurs in the protein structure in the vicinity of the active site involving positional and conformational changes in some amino acid residues, a change in the V coenzyme conformation, addition of new hydration sites, and elimination of others. These changes culminate in an increase in the number of hydrogen bonds to the protein, explaining the greater affinity of the apoenzyme for ThTDP. The observed hydrogen bonding pattern is not an invariant feature of ThDP-dependent enzymes but rather specific to this enzyme since the extra hydrogen bonds are made with nonconserved residues. Accordingly, these sequence-related hydrogen bonding differences likewise explain the wide variation in the affinities of different thiamin-dependent enzymes for ThTDP and ThDP. The sequence of each enzyme determines its ability to form hydrogen bonds to the inhibitor or cofactor. Mechanistic roles are suggested for the aforementioned reorganization and its reversal in PDHc E1 catalysis: to promote substrate binding and product release. This study also provides additional insight into the role of water in enzyme inhibition and catalysis.
About this Structure
1RP7 is a Single protein structure of sequence from Escherichia coli, and escherichia coli o157:h7. Full crystallographic information is available from OCA.
Reference
Structural determinants of enzyme binding affinity: the E1 component of pyruvate dehydrogenase from Escherichia coli in complex with the inhibitor thiamin thiazolone diphosphate., Arjunan P, Chandrasekhar K, Sax M, Brunskill A, Nemeria N, Jordan F, Furey W, Biochemistry. 2004 Mar 9;43(9):2405-11. PMID:14992577 Page seeded by OCA on Sat May 3 07:44:55 2008
