PDBsum entry 1dr3

Oxidoreductase

PDB id

1dr3

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Contents

			Protein chain

					186 a.a. *

			Ligands

					TAP


					HBI

			Metals

					_CA

			Waters ×110

* Residue conservation analysis

PDB id:

1dr3

Links

Name:

Oxidoreductase

Title:

2.3 angstroms crystal structure of chicken liver dihydrofolate reductase complexed with thionadp+ and biopterin

Structure:

Dihydrofolate reductase. Chain: a. Engineered: yes

Source:

Gallus gallus. Chicken. Organism_taxid: 9031. Organ: liver

Resolution:

2.30Å

R-factor:

0.140

Authors:

M.A.Mctigue,J.F.Davies /Ii,B.T.Kaufman,N.-H.Xuong,J.Kraut

Key ref:

M.A.McTigue et al. (1993). Crystal structures of chicken liver dihydrofolate reductase: binary thioNADP+ and ternary thioNADP+.biopterin complexes. Biochemistry, 32, 6855-6862. PubMed id: 8334118 DOI: 10.1021/bi00078a008

Date:

14-Mar-92

Release date:

31-Oct-93

PROCHECK

	Headers

	References

Protein chain

P00378 (DYR_CHICK) - Dihydrofolate reductase from Gallus gallus

Seq: Struc:					189 a.a. 186 a.a.

Key:

Secondary structure

CATH domain



		Enzyme reactions

Enzyme class:

E.C.1.5.1.3 - dihydrofolate reductase.

[IntEnz] [ExPASy] [KEGG] [BRENDA]

Pathway:

Folate Coenzymes

Reaction:

(6S)-5,6,7,8-tetrahydrofolate + NADP⁺ = 7,8-dihydrofolate + NADPH + H⁺

(6S)-5,6,7,8-tetrahydrofolate

NADP(+)
Bound ligand (Het Group name = TAP)
matches with 95.92% similarity

7,8-dihydrofolate

NADPH

H(+)

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

reference

DOI no: 10.1021/bi00078a008	Biochemistry 32:6855-6862 (1993)
PubMed id: 8334118

Crystal structures of chicken liver dihydrofolate reductase: binary thioNADP+ and ternary thioNADP+.biopterin complexes.
M.A.McTigue, J.F.Davies, B.T.Kaufman, J.Kraut.

ABSTRACT

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)

Literature references that cite this PDB file's key reference

PubMed id

Reference

18487202

R.P.Ilagan, M.Tiso, D.W.Konas, C.Hemann, D.Durra, R.Hille, and D.J.Stuehr (2008).
Differences in a conformational equilibrium distinguish catalysis by the endothelial and neuronal nitric-oxide synthase flavoproteins.

J Biol Chem, 283, 19603-19615.

12791694

A.Singh, J.D.Venning, P.G.Quirk, G.I.van Boxel, D.J.Rodrigues, S.A.White, and J.B.Jackson (2003).
Interactions between transhydrogenase and thio-nicotinamide Analogues of NAD(H) and NADP(H) underline the importance of nucleotide conformational changes in coupling to proton translocation.

J Biol Chem, 278, 33208-33216.

PDB codes:

1pt9 1ptj

12660990

P.Shrimpton, A.Mullaney, and R.K.Allemann (2003).
Functional role for Tyr 31 in the catalytic cycle of chicken dihydrofolate reductase.

Proteins, 51, 216-223.

12136140

Y.Q.Shen, S.Y.Song, and Z.J.Lin (2002).
Structures of D-glyceraldehyde-3-phosphate dehydrogenase complexed with coenzyme analogues.

Acta Crystallogr D Biol Crystallogr, 58, 1287-1297.

PDB codes:

1ihx 1ihy

10997901

T.Doukov, J.Seravalli, J.J.Stezowski, and S.W.Ragsdale (2000).
Crystal structure of a methyltetrahydrofolate- and corrinoid-dependent methyltransferase.

Structure, 8, 817-830.

PDB code:

1f6y

9875848

C.S.Raman, H.Li, P.Martásek, V.Král, B.S.Masters, and T.L.Poulos (1998).
Crystal structure of constitutive endothelial nitric oxide synthase: a paradigm for pterin function involving a novel metal center.

Cell, 95, 939-950.

PDB codes:

1nse 2nse 3nse 4nse

8762136

K.K.Koretke, Z.Luthey-Schulten, and P.G.Wolynes (1996).
Self-consistently optimized statistical mechanical energy functions for sequence structure alignment.

Protein Sci, 5, 1043-1059.

The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB codes are shown on the right.