2j9l | pdb_00002j9l

Cytoplasmic Domain of the Human Chloride Transporter ClC-5 in complex with ATP

spinqualitylabelsall models 2j9l, resolution 2.30Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2j9l is a 6 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.3Å Ligands: ATP, CL Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease CLCN5_HUMAN Defects in CLCN5 are a cause of hypophosphatemic rickets, X-linked recessive (XLRHR) [MIM:300554. XLRHR is a renal disease belonging to the 'Dent disease complex', a group of disorders characterized by proximal renal tubular defect, hypercalciuria, nephrocalcinosis, and renal insufficiency. The spectrum of phenotypic features is remarkably similar in the various disorders, except for differences in the severity of bone deformities and renal impairment. XLRH patients present with rickets or osteomalacia, hypophosphatemia due to decreased renal tubular phosphate reabsorption, hypercalciuria, and low molecular weight proteinuria. Patients develop nephrocalcinosis with progressive renal failure in adulthood. Female carriers may have asymptomatic hypercalciuria or hypophosphatemia only. Defects in CLCN5 are the cause of nephrolithiasis type 2 (NPHL2) [MIM:300009; also known as Dent disease 1. NPHL2 is an X-linked recessive renal disease belonging to the 'Dent disease complex'. NPHL2 patients manifest hypercalciuria, hypophosphatemia, aminoaciduria, nephrocalcinosis and nephrolithiasis, renal insufficiency leading to renal failure in adulthood, rickets (33% of patients) and osteomalacia. Defects in CLCN5 are the cause of nephrolithiasis type 1 (NPHL1) [MIM:310468; also designated XRN. NPHL1 is an X-linked recessive renal disease belonging to the 'Dent disease complex'. NPHL1 presents with hypercalciuria, nephrocalcinosis, renal stones and renal insufficiency. Patients lack urinary acidification defects, rickets, and osteomalacia. Defects in CLCN5 are the cause of low molecular weight proteinuria with hypercalciuria and nephrocalcinosis (LMWPHN) [MIM:308990. LMWPHN is an X-linked renal disease belonging to the 'Dent disease complex'. Patients tend to have hypercalciuric nephrocalcinosis without rickets or renal failure. Function CLCN5_HUMAN Proton-coupled chloride transporter. Functions as antiport system and exchanges chloride ions against protons. Important for normal acidification of the endosome lumen. May play an important role in renal tubular function. 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 PubMed The ubiquitous CBS domains, which are found as part of cytoplasmic domains in the ClC family of chloride channels and transporters, have previously been identified as building blocks for regulatory nucleotide-binding sites. Here we report the structures of the cytoplasmic domain of the human transporter ClC-5 in complex with ATP and ADP. The nucleotides bind to a specific site in the protein. As determined by equilibrium dialysis, the affinities for ATP, ADP and AMP are in the high micromolar range. Point mutations that interfere with nucleotide binding change the transport behavior of a ClC-5 mutant expressed in Xenopus laevis oocytes. Our results establish the structural and energetic basis for the interaction of ClC-5 with nucleotides and provide a framework for future investigations. Nucleotide recognition by the cytoplasmic domain of the human chloride transporter ClC-5.,Meyer S, Savaresi S, Forster IC, Dutzler R Nat Struct Mol Biol. 2007 Jan;14(1):60-7. Epub 2006 Dec 31. PMID:17195847 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Ion channels 3D structures

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