1zp3

From Proteopedia

---

Revision as of 05:27, 21 November 2007

proteopedia linkproteopedia link

spinqualitylabelsall models 1zp3, resolution 1.85Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

E. coli Methylenetetrahydrofolate Reductase (oxidized)

Overview

Methylenetetrahydrofolate reductases (MTHFRs; EC 1.7.99.5) catalyze the, NAD(P)H-dependent reduction of 5,10-methylenetetrahydrofolate, (CH(2)-H(4)folate) to 5-methyltetrahydrofolate (CH(3)-H(4)folate) using, flavin adenine dinucleotide (FAD) as a cofactor. The initial X-ray, structure of Escherichia coli MTHFR revealed that this 33-kDa polypeptide, is a (betaalpha)(8) barrel that aggregates to form an unusual tetramer, with only 2-fold symmetry. Structures of reduced enzyme complexed with, NADH and of oxidized Glu28Gln enzyme complexed with CH(3)-H(4)folate have, now been determined at resolutions of 1.95 and 1.85 A, respectively. The, NADH complex reveals a rare mode of dinucleotide binding; NADH adopts a, hairpin conformation and is sandwiched between a conserved phenylalanine, Phe223, and the isoalloxazine ring of FAD. The nicotinamide of the bound, pyridine nucleotide is stacked against the si face of the flavin ring with, C4 adjoining the N5 of FAD, implying that this structure models a complex, that is competent for hydride transfer. In the complex with, CH(3)-H(4)folate, the pterin ring is also stacked against FAD in an, orientation that is favorable for hydride transfer. Thus, the binding, sites for the two substrates overlap, as expected for many enzymes that, catalyze ping-pong reactions, and several invariant residues interact with, both folate and pyridine nucleotide substrates. Comparisons of liganded, and substrate-free structures reveal multiple conformations for the loops, beta2-alpha2 (L2), beta3-alpha3 (L3), and beta4-alpha4 (L4) and suggest, that motions of these loops facilitate the ping-pong reaction. In, particular, the L4 loop adopts a "closed" conformation that allows Asp120, to hydrogen bond to the pterin ring in the folate complex but must move to, an "open" conformation to allow NADH to bind.

About this Structure

1ZP3 is a Single protein structure of sequence from Escherichia coli with SO4, FAD and MPD as ligands. Active as Deleted entry, with EC number 1.7.99.5 Full crystallographic information is available from OCA.

Reference

Structures of NADH and CH3-H4folate complexes of Escherichia coli methylenetetrahydrofolate reductase reveal a spartan strategy for a ping-pong reaction., Pejchal R, Sargeant R, Ludwig ML, Biochemistry. 2005 Aug 30;44(34):11447-57. PMID:16114881

Page seeded by OCA on Wed Nov 21 07:35:03 2007