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| {{STRUCTURE_1dr3| PDB=1dr3 | SCENE= }} | | {{STRUCTURE_1dr3| PDB=1dr3 | SCENE= }} |
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| '''2.3 ANGSTROMS CRYSTAL STRUCTURE OF CHICKEN LIVER DIHYDROFOLATE REDUCTASE COMPLEXED WITH THIONADP+ AND BIOPTERIN'''
| | ===2.3 ANGSTROMS CRYSTAL STRUCTURE OF CHICKEN LIVER DIHYDROFOLATE REDUCTASE COMPLEXED WITH THIONADP+ AND BIOPTERIN=== |
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| ==Overview==
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| The role of the 3'-carboxamide substituent of NADPH in the reduction of pteridine substrates as catalyzed by dihydrofolate reductase (EC 1.5.1.3, DHFR) has been investigated by determining crystal structures at 2.3 A of chicken liver DHFR in a binary complex with oxidized thionicotinamide adenine dinucleotide (thioNADP+) and in a ternary complex with thioNADP+ and biopterin. These structures are isomorphous with those previously reported for chicken liver DHFR [Volz, K.W., Matthews, D.A., Alden, R.A., Freer, S. T., Hansch, C., Kaufman, B. T., & Kraut, J. (1982) J. Biol. Chem. 257, 2528-2536]. ThioNADPH, which has a 3'-carbothioamide substituent in place of a 3'-carboxamide, functions very poorly as a coenzyme for DHFR [Williams, T. J., Lee, T. K., & Dunlap, R. B. (1977) Arch, Biochem. Biophys. 181, 569-579; Stone, S. R., Mark, A., & Morrison, J. F. (1984) Biochemistry 23, 4340-4346]. Comparisons show that, while NADP+ and NADPH bind to DHFR with the pyridine ring and 3'-carboxamide coplanar, the thioamide group is twisted by 23 degrees from the pyridine plane in both the binary and ternary complexes. This twist appears to be due to steric conflict between the thioamide sulfur atom and both the pyridine ring at C4 and the adjacent protein backbone at Ala-9. It results in an unfavorably close contact between the sulfur and the biopterin pteridine ring (0.9 A less than the van der Waals separation) which, on the basis of the refined structure, greatly destabilizes the binding of biopterin.(ABSTRACT TRUNCATED AT 250 WORDS) | | The line below this paragraph, {{ABSTRACT_PUBMED_8334118}}, adds the Publication Abstract to the page |
| | (as it appears on PubMed at http://www.pubmed.gov), where 8334118 is the PubMed ID number. |
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| | {{ABSTRACT_PUBMED_8334118}} |
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| ==About this Structure== | | ==About this Structure== |
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| [[Category: Xuong, N H.]] | | [[Category: Xuong, N H.]] |
| [[Category: Oxidoreductase]] | | [[Category: Oxidoreductase]] |
| ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 14:10:47 2008'' | | |
| | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jun 30 23:29:53 2008'' |
