2JKY: Saccharomyces Cerevisiae Hypoxanthine-Guanine Phosphoribosyltransferase In Complex With Gmp (Guanosine 5' -Monophosphate) (Tetragonal Crystal Form)

Citation:
Abstract
Hypoxanthine-guanine phosphoribosyltransferase (HGPRT) is a key enzyme of the purine recycling pathway that catalyzes the conversion of 5-phospho-ribosyl-alpha-1-pyrophosphate and guanine or hypoxanthine to guanosine monophosphate (GMP) or inosine monophosphate (IMP), respectively, and pyrophosphate (PPi). We report the first crystal structure of a fungal 6-oxopurine phosphoribosyltransferase, the Saccharomyces cerevisiae HGPRT (Sc-HGPRT) in complex with GMP. The crystal structures of full length protein with (WT1) or without (WT2) sulfate that mimics the phosphate group in the PPi binding site were solved by molecular replacement using the structure of a truncated version (Delta7) solved beforehand by multiwavelength anomalous diffusion. Sc-HGPRT is a dimer and adopts the overall structure of class I phosphoribosyltransferases (PRTs) with a smaller hood domain and a short two-stranded parallel beta-sheet linking the N- to the C-terminal end. The catalytic loops in WT1 and WT2 are in an open form while in Delta7, due to an inter-subunit disulfide bridge, the catalytic loop is in either an open or closed form. The closure is concomitant with a peptide plane flipping in the PPi binding loop. Moreover, owing the flexibility of a GGGG motif conserved in fungi, all the peptide bonds of the phosphate binding loop are in trans conformation whereas in nonfungal 6-oxopurine PRTs, one cis-peptide bond is required for phosphate binding. Mutations affecting the enzyme activity or the previously characterized feedback inhibition by GMP are located at the nucleotide binding site and the dimer interface.
PDB ID: 2JKYDownload
MMDB ID: 78086
PDB Deposition Date: 2008/9/2
Updated in MMDB: 2009/11
Experimental Method:
x-ray diffraction
Resolution: 2.3  Å
Source Organism:
Similar Structures:
Biological Unit for 2JKY: dimeric; determined by author and by software (PISA)
Molecular Components in 2JKY
Label Count Molecule
Proteins (2 molecules)
2
Hypoxanthine-guanine Phosphoribosyltransferase(Gene symbol: HPT1)
Molecule annotation
Chemicals (5 molecules)
1
2
2
2
3
1
* Click molecule labels to explore molecular sequence information.

Citing MMDB
.