5-FTHF is a metabolite of the one-carbon

5-FTHF is a metabolite of the one-carbon transfer reaction selleck chemicals catalysed by 5-formyltetrahydrofolate cyclo-ligase. Kinetic studies show that 5-FTHF is a weak inhibitor of EfTS, suggesting that the EfTS-5-FTHF complex may function as a source of folates and/or may regulate one-carbon metabolism. The structure represents the first example of endogenous 5-FTHF bound to a protein selleckchem involved in folate metabolism.
The crystal structure of the 11.14 kDa orphan ORF 1382 from Archaeoglobus fulgidus (AF1382) has been determined by sulfur SAD phasing using a moderately diffracting crystal and 1.9 angstrom wavelength synchrotron X-rays. AF1382 was selected as a structural genomics target by the Southeast Collaboratory for Structural Inhibitors,Modulators,Libraries Genomics (SECSG) since sequence analyses showed that it did not belong to the Pfam-A database and thus could represent a novel fold.

The structure was determined by exploiting longer wavelength X-rays and data redundancy to increase the anomalous signal in the data. AF1382 is a 95-residue Inhibitors,Modulators,Libraries protein containing five S atoms associated with four methionine residues Inhibitors,Modulators,Libraries and a single cysteine residue that yields a calculated Bijvoet ratio (Delta F-anom/F) of Inhibitors,Modulators,Libraries 1.39% for 1.9 angstrom wavelength X-rays. Coupled with an average Bijvoet redundancy of 25 (two 360 degrees data sets), this produced an excellent electron-density map that allowed 69 of the 95 residues to be automatically fitted. The S-SAD model was then manually completed and refined (R = 23.2%, R-free = 26.8%) to 2.3 angstrom resolution (PDB entry 3o3k).

High-resolution data were subsequently collected from a better diffracting crystal using 0.

97 angstrom wavelength synchrotron Inhibitors,Modulators,Libraries X-rays and the S-SAD model was refined (R = 17.9%, Inhibitors,Modulators,Libraries R-free = 21.4%) to 1.85 angstrom resolution (PDB entry 3ov8). AF1382 Inhibitors,Modulators,Libraries has a winged-helix-turn-helix structure common to many DNA-binding proteins and most closely resembles the N-terminal domain (residues 1-82) of the Rio2 kinase from A. fulgidus, which has been shown to bind DNA, and a number of MarR-family transcriptional regulators, suggesting a similar DNA-binding function for AF1382. The analysis also points out the advantage gained from carrying out data reduction and structure determination on-site while the crystal is still available for further data collection.

Zinc is a suitable metal for anomalous dispersion phasing methods in protein crystallography.

Inhibitors,Modulators,Libraries Structure determination using zinc anomalous Inhibitors,Modulators,Libraries Inhibitors,Modulators,Libraries scattering has been almost exclusively limited to proteins with intrinsically bound zinc(s). Here, inhibitor AT101 it is reported that multiple zinc ions can easily be charged onto the surface of proteins with no intrinsic zinc-binding site by using zinc-containing solutions. Zn derivatization of protein surfaces appears to be a largely unnoticed but promising method of protein structure Sorafenib PDGFR inhibitor determination.

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