2JBH

Human phosphoribosyl transferase domain containing 1

PDB DOI: https://doi.org/10.2210/pdb2JBH/pdb

Classification: TRANSFERASE
Organism(s): Homo sapiens
Expression System: Escherichia coli BL21(DE3)
Mutation(s): No

Deposited: 2006-12-07 Released: 2006-12-20
Deposition Author(s): Welin, M., Stenmark, P., Arrowsmith, C., Berglund, H., Busam, R., Collins, R., Edwards, A., Eklund, H., Ericsson, U.B., Flodin, S., Flores, A., Graslund, S., Hammarstrom, M., Hallberg, B.M., Holmberg Schiavone, L., Hogbom, M., Johansson, I., Karlberg, T., Kotenyova, T., Moche, M., Nilsson, M.E., Nyman, T., Ogg, D., Persson, C., Sagemark, J., Sundstrom, M., Uppenberg, J., Thorsell, A.G., Van Den Berg, S., Weigelt, J., Nordlund, P.

Experimental Data Snapshot

Method: X-RAY DIFFRACTION
Resolution: 1.70 ?
R-Value Free: 0.215
R-Value Work: 0.182
R-Value Observed: 0.184

Starting Model: experimental
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wwPDB Validation 3D Report Full Report

Ligand Structure Quality Assessment

This is version 1.4 of the entry. See complete history.

Literature

Structural and Functional Studies of the Human Phosphoribosyltransferase Domain Containing Protein 1.

Welin, M., Egeblad, L., Johansson, A., Stenmark, P., Wang, L., Flodin, S., Nyman, T., Tresaugues, L., Kotenyova, T., Johansson, I., Eriksson, S., Eklund, H., Nordlund, P.

(2010) FEBS J 277: 4920

PubMed: 21054786 Search on PubMed
DOI: https://doi.org/10.1111/j.1742-4658.2010.07897.x
Primary Citation of Related Structures:
2JBH

PubMed Abstract:
Human hypoxanthine-guanine phosphoribosyltransferase (HPRT) (EC 2.4.2.8) catalyzes the conversion of hypoxanthine and guanine to their respective nucleoside monophosphates. Human HPRT deficiency as a result of genetic mutations is linked to both Lesch-Nyhan disease and gout. In the present study, we have characterized phosphoribosyltransferase domain containing protein 1 (PRTFDC1), a human HPRT homolog of unknown function. The PRTFDC1 structure has been determined at 1.7 ? resolution with bound GMP. The overall structure and GMP binding mode are very similar to that observed for HPRT. Using a thermal-melt assay, a nucleotide metabolome library was screened against PRTFDC1 and revealed that hypoxanthine and guanine specifically interacted with the enzyme. It was subsequently confirmed that PRTFDC1 could convert these two bases into their corresponding nucleoside monophosphate. However, the catalytic efficiency (k(cat)/K(m)) of PRTFDC1 towards hypoxanthine and guanine was only 0.26% and 0.09%, respectively, of that of HPRT. This low activity could be explained by the fact that PRTFDC1 has a Gly in the position of the proposed catalytic Asp of HPRT. In PRTFDC1, a water molecule at the position of the aspartic acid side chain position in HPRT might be responsible for the low activity observed by acting as a weak base. The data obtained in the present study indicate that PRTFDC1 does not have a direct catalytic role in the nucleotide salvage pathway.

Organizational Affiliation

Structural Genomics Consortium, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.

Macromolecule Content

Total Structure Weight: 52.7 kDa
Atom Count: 3,799
Modelled Residue Count: 421
Deposited Residue Count: 450
Unique protein chains: 1

Macromolecules

Find similar proteins by:

(by identity cutoff) | 3D Structure

Entity ID: 1
Molecule	Chains	Sequence Length	Organism	Details	Image
PHOSPHORIBOSYLTRANSFERASE DOMAIN-CONTAINING PROTEIN 1	A, B	225	Homo sapiens	Mutation(s): 0 Gene Names: PRTFDC1 EC: 2.4.2.8
UniProt & NIH Common Fund Data Resources
Find proteins for Q9NRG1 (Homo sapiens) Explore Q9NRG1 Go to UniProtKB: Q9NRG1
PHAROS: Q9NRG1 GTEx: ENSG00000099256
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Group	Q9NRG1
Sequence Annotations Expand
Reference Sequence

Small Molecules

Ligands 3 Unique
ID	Chains	Name / Formula / InChI Key	2D Diagram	3D Interactions
5GP Query on 5GP Download Ideal Coordinates CCD File SDF format, chain F [auth A] SDF format, chain J [auth B] MOL2 format, chain F [auth A] MOL2 format, chain J [auth B] mmCIF format, chain F [auth A] mmCIF format, chain J [auth B]	F [auth A], J [auth B]	GUANOSINE-5'-MONOPHOSPHATE C₁₀ H₁₄ N₅ O₈ P RQFCJASXJCIDSX-UUOKFMHZSA-N		Interactions Focus chain F [auth A] Focus chain J [auth B] Interactions & Density Focus chain F [auth A] Focus chain J [auth B]
PO4 Query on PO4 Download Ideal Coordinates CCD File SDF format, chain C [auth A] SDF format, chain G [auth B] MOL2 format, chain C [auth A] MOL2 format, chain G [auth B] mmCIF format, chain C [auth A] mmCIF format, chain G [auth B]	C [auth A], G [auth B]	PHOSPHATE ION O₄ P NBIIXXVUZAFLBC-UHFFFAOYSA-K		Interactions Focus chain C [auth A] Focus chain G [auth B] Interactions & Density Focus chain C [auth A] Focus chain G [auth B]
CA Query on CA Download Ideal Coordinates CCD File SDF format, chain D [auth A] SDF format, chain E [auth A] SDF format, chain H [auth B] SDF format, chain I [auth B] MOL2 format, chain D [auth A] MOL2 format, chain E [auth A] MOL2 format, chain H [auth B] MOL2 format, chain I [auth B] mmCIF format, chain D [auth A] mmCIF format, chain E [auth A] mmCIF format, chain H [auth B] mmCIF format, chain I [auth B]	D [auth A], E [auth A], H [auth B], I [auth B]	CALCIUM ION Ca BHPQYMZQTOCNFJ-UHFFFAOYSA-N		Interactions Focus chain D [auth A] Focus chain E [auth A] Focus chain H [auth B] Focus chain I [auth B] Interactions & Density Focus chain D [auth A] Focus chain E [auth A] Focus chain H [auth B] Focus chain I [auth B]

Modified Residues 1 Unique
ID	Chains	Type	Formula	2D Diagram	Parent
CAS Query on CAS	A, B	L-PEPTIDE LINKING	C₅ H₁₂ As N O₂ S		CYS

Experimental Data & Validation

Experimental Data

Method: X-RAY DIFFRACTION
Resolution: 1.70 ?
R-Value Free: 0.215
R-Value Work: 0.182
R-Value Observed: 0.184
Space Group: P 3 2 1

Unit Cell:

Length ( ? )	Angle ( ? )
a = 139.232	α = 90
b = 139.232	β = 90
c = 52.132	γ = 120

Software Package:

Software Name	Purpose
REFMAC	refinement
MOSFLM	data reduction
SCALA	data scaling
MOLREP	phasing

Structure Validation

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Ligand Structure Quality Assessment

Entry History

Deposition Data

Released Date: 2006-12-20

Deposition Author(s):

Holmberg Schiavone, L.

Revision History (Full details and data files)

Version 1.0: 2006-12-20
Type: Initial release
Version 1.1: 2011-05-08
Changes: Version format compliance
Version 1.2: 2011-07-13
Changes: Version format compliance
Version 1.3: 2023-12-13
Changes: Data collection, Database references, Derived calculations, Other, Refinement description
Version 1.4: 2024-10-23
Changes: Structure summary