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PDBsum entry 1dr4
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Oxidoreductase
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PDB id
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1dr4
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References listed in PDB file
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Key reference
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Title
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Crystal structures of chicken liver dihydrofolate reductase: binary thionadp+ and ternary thionadp+.Biopterin complexes.
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Authors
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M.A.Mctigue,
J.F.Davies,
B.T.Kaufman,
J.Kraut.
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Ref.
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Biochemistry, 1993,
32,
6855-6862.
[DOI no: ]
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PubMed id
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Note In the PDB file this reference is
annotated as "TO BE PUBLISHED".
The citation details given above were identified by an automated
search of PubMed on title and author
names, giving a
percentage match of
72%.
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Abstract
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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)
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Secondary reference #1
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Title
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Crystal structures of recombinant human dihydrofolate reductase complexed with folate and 5-Deazafolate.
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Authors
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J.F.Davies,
T.J.Delcamp,
N.J.Prendergast,
V.A.Ashford,
J.H.Freisheim,
J.Kraut.
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Ref.
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Biochemistry, 1990,
29,
9467-9479.
[DOI no: ]
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PubMed id
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Secondary reference #2
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Title
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Refined crystal structures of escherichia coli and chicken liver dihydrofolate reductase containing bound trimethoprim.
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Authors
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D.A.Matthews,
J.T.Bolin,
J.M.Burridge,
D.J.Filman,
K.W.Volz,
B.T.Kaufman,
C.R.Beddell,
J.N.Champness,
D.K.Stammers,
J.Kraut.
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Ref.
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J Biol Chem, 1985,
260,
381-391.
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PubMed id
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Secondary reference #3
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Title
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Dihydrofolate reductase. The stereochemistry of inhibitor selectivity.
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Authors
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D.A.Matthews,
J.T.Bolin,
J.M.Burridge,
D.J.Filman,
K.W.Volz,
J.Kraut.
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Ref.
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J Biol Chem, 1985,
260,
392-399.
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PubMed id
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Secondary reference #4
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Title
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Crystal structure of avian dihydrofolate reductase containing phenyltriazine and NADPH.
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Authors
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K.W.Volz,
D.A.Matthews,
R.A.Alden,
S.T.Freer,
C.Hansch,
B.T.Kaufman,
J.Kraut.
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Ref.
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J Biol Chem, 1982,
257,
2528-2536.
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PubMed id
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Secondary reference #5
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Title
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Primary structure of chicken liver dihydrofolate reductase.
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Authors
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A.A.Kumar,
D.T.Blankenship,
B.T.Kaufman,
J.H.Freisheim.
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Ref.
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Biochemistry, 1980,
19,
667-678.
[DOI no: ]
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PubMed id
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