PDBsum entry 1h6h

Px domain

PDB id: 1h6h

Contents

Protein chain

143 a.a. *

Ligands

PIB

GOL

Waters ×182

* Residue conservation analysis

PDB id:

1h6h

Name:

Px domain

Title:

Structure of the px domain from p40phox bound to phosphatidylinositol 3-phosphate

Structure:

Neutrophil cytosol factor 4. Chain: a. Fragment: px domain residues 2-144. Synonym: ncf-4, neutrophil NADPH oxidase factor 4, p40-phox, p40phox. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Cell: neutrophil. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008. Expression_system_variant: c41.

Resolution:

1.70Å R-factor: 0.196 R-free: 0.232

Authors:

D.Karathanassis,J.Bravo,M.Pacold,O.Perisic,R.L.Williams

Key ref:

J.Bravo et al. (2001). The crystal structure of the PX domain from p40(phox) bound to phosphatidylinositol 3-phosphate. Mol Cell, 8, 829-839. PubMed id: 11684018 DOI: 10.1016/S1097-2765(01)00372-0

Date:

15-Jun-01 Release date: 01-Nov-01

Protein chain

Q15080  (NCF4_HUMAN) -  Neutrophil cytosol factor 4 from Homo sapiens

Seq: 339 a.a.

Struc: 143 a.a.

DOI no: 10.1016/S1097-2765(01)00372-0

Mol Cell 8:829-839 (2001)

PubMed id: 11684018

The crystal structure of the PX domain from p40(phox) bound to phosphatidylinositol 3-phosphate.

J.Bravo, D.Karathanassis, C.M.Pacold, M.E.Pacold, C.D.Ellson, K.E.Anderson, P.J.Butler, I.Lavenir, O.Perisic, P.T.Hawkins, L.Stephens, R.L.Williams.

ABSTRACT

More than 50 human proteins with a wide range of functions have a 120 residue phosphoinositide binding module known as the PX domain. The 1.7 A X-ray crystal structure of the PX domain from the p40(phox) subunit of NADPH oxidase bound to PtdIns(3)P shows that the PX domain embraces the 3-phosphate on one side of a water-filled, positively charged pocket and reveals how 3-phosphoinositide specificity is achieved. A chronic granulomatous disease (CGD)-associated mutation in the p47(phox) PX domain that abrogates PtdIns(3)P binding maps to a conserved Arg that does not directly interact with the phosphoinositide but instead appears to stabilize a critical lipid binding loop. The SH3 domain present in the full-length protein does not affect soluble PtdIns(3)P binding to the p40(phox) PX domain.

Selected figure(s)

Figure 5.
Figure 5. PtdIns(3)P Bound to the p40^phoxPX Domain(A) σ[A]-weighted electron density for the di-C4-PtdIns(3)P and some of the surrounding amino acids. The 2mF[o]-DF[c] map was contoured at 1 σ and rendered with BOBSCRIPT (Esnouf, 1999).(B) A view of the PtdIns(3)P binding pocket. Interacting residues are drawn as cyan sticks, and hydrogen bonds are shown by dashed lines. The inositol ring also makes hydrophobic contacts with the side chain of Tyr59, and the diacylglycerol moiety makes hydrophobic contacts with the side chain of Tyr94. In addition, the Arg57/Asp139 salt link is shown

Figure 7.
Figure 7. Comparison of Three Phosphoinositide Binding ModulesThe phosphoinositide binding sites in the EEA1 FYVE domain (PDB: 1hyi) (Kutateladze and Overduin, 2001), the p40^phox PX domain, and the Grp1 PH domain (PDB: 1fgy) (Lietzke et al., 2000) are shown. To illustrate the binding environments, the structures were superimposed using their inositol rings. The molecular surfaces are colored by electrostatic potential.(A) The EEA1 FYVE domain with PtdIns(3)P bound in a basic pocket.(B) The p40^phox PX domain. The PtdIns(3)P sits in a basic pocket that interacts with one face of the ring, while the other face is exposed to the solvent.(C) The Grp1 PH domain bound to Ins(1,3,4,5)P[4]. As with the p40^phox PX domain, only one face of the inositol ring interacts with a basic patch on the surface of the domain

The above figures are reprinted by permission from Cell Press: Mol Cell (2001, 8, 829-839) copyright 2001.

Figures were selected by an automated process.