2dyb
From Proteopedia
The crystal structure of human p40(phox)
Structural highlights
Disease[NCF4_HUMAN] Defects in NCF4 are the cause of chronic granulomatous disease autosomal recessive cytochrome-b-positive type 3 (CGD3) [MIM:613960]. CGD3 is a disorder characterized by the inability of neutrophils and phagocytes to kill microbes that they have ingested. Patients suffer from life-threatening bacterial/fungal infections.[1] Function[NCF4_HUMAN] Component of the NADPH-oxidase, a multicomponent enzyme system responsible for the oxidative burst in which electrons are transported from NADPH to molecular oxygen, generating reactive oxidant intermediates. It may be important for the assembly and/or activation of the NADPH-oxidase complex. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedThe superoxide-producing phagocyte NADPH oxidase is activated during phagocytosis to destroy ingested microbes. The adaptor protein p40phox associates via the PB1 domain with the essential oxidase activator p67phox, and is considered to function by recruiting p67phox to phagosomes; in this process, the PX domain of p40phox binds to phosphatidylinositol 3-phosphate [PtdIns(3)P], a lipid abundant in the phagosomal membrane. Here we show that the PtdIns(3)P-binding activity of p40phox is normally inhibited by the PB1 domain both in vivo and in vitro. The crystal structure of the full-length p40phox reveals that the inhibition is mediated via intramolecular interaction between the PB1 and PX domains. The interface of the p40phox PB1 domain for the PX domain localizes on the opposite side of that for the p67phox PB1 domain, and thus the PB1-mediated PX regulation occurs without preventing the PB1-PB1 association with p67phox. Full-length p40phox structure suggests a basis for regulation mechanism of its membrane binding.,Honbou K, Minakami R, Yuzawa S, Takeya R, Suzuki NN, Kamakura S, Sumimoto H, Inagaki F EMBO J. 2007 Feb 21;26(4):1176-86. Epub 2007 Feb 8. PMID:17290225[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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