PDBsum entry 2cbz

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protein ligands metals links
Transport PDB id
Jmol PyMol
Protein chain
231 a.a. *
Waters ×284
* Residue conservation analysis
PDB id:
Name: Transport
Title: Structure of the human multidrug resistance protein 1 nucleotide binding domain 1
Structure: Multidrug resistance-associated protein 1. Chain: a. Fragment: nbd1 domain, residues 642-871. Synonym: mrp1, atp-binding cassette sub- family c member 1. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 469008.
1.50Å     R-factor:   0.161     R-free:   0.187
Authors: O.Ramaen,N.Leulliot,C.Sizun,N.Ulryck,O.Pamlard, J.-Y.Lallemand,H.Van Tilbeurgh,E.Jacquet
Key ref:
O.Ramaen et al. (2006). Structure of the human multidrug resistance protein 1 nucleotide binding domain 1 bound to Mg2+/ATP reveals a non-productive catalytic site. J Mol Biol, 359, 940-949. PubMed id: 16697012 DOI: 10.1016/j.jmb.2006.04.005
10-Jan-06     Release date:   17-May-06    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
P33527  (MRP1_HUMAN) -  Multidrug resistance-associated protein 1
1531 a.a.
231 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     integral to membrane   1 term 
  Biological process     transmembrane transport   1 term 
  Biochemical function     ATP binding     3 terms  


DOI no: 10.1016/j.jmb.2006.04.005 J Mol Biol 359:940-949 (2006)
PubMed id: 16697012  
Structure of the human multidrug resistance protein 1 nucleotide binding domain 1 bound to Mg2+/ATP reveals a non-productive catalytic site.
O.Ramaen, N.Leulliot, C.Sizun, N.Ulryck, O.Pamlard, J.Y.Lallemand, H.Tilbeurgh, E.Jacquet.
Human multidrug resistance protein 1 (MRP1) is a membrane protein that belongs to the ATP-binding cassette (ABC) superfamily of transport proteins. MRP1 contributes to chemotherapy failure by exporting a wide range of anti-cancer drugs when over expressed in the plasma membrane of cells. Here, we report the first high-resolution crystal structure of human MRP1-NBD1. Drug efflux requires energy resulting from hydrolysis of ATP by nucleotide binding domains (NBDs). Contrary to the prokaryotic NBDs, the extremely low intrinsic ATPase activity of isolated MRP1-NBDs allowed us to obtain the structure of wild-type NBD1 in complex with Mg2+/ATP. The structure shows that MRP1-NBD1 adopts a canonical fold, but reveals an unexpected non-productive conformation of the catalytic site, providing an explanation for the low intrinsic ATPase activity of NBD1 and new hypotheses on the cooperativity of ATPase activity between NBD1 and NBD2 upon heterodimer formation.
  Selected figure(s)  
Figure 1.
Figure 1. Stereo ribbon representation of MRP1–NBD1. (a) The F1-like ATP-binding core is shown in red, the specific ABC-β sub-domain in orange, the central helix H1 in blue, helix H6 in cyan, helices H8 and H9 in magenta and the ABC-α sub-domain in green. The ATP is represented in sticks and the F[o]−F[c] map contoured at 3σ is shown around the ATP. (b) ATP binding site. The residues in contact with ATP are shown in stick representation. Figures are generated using Pymol (DeLano, W.L. The PyMOL Molecular Graphics System (2002) Web site
Figure 4.
Figure 4. Conformation of the His/Asp-Glu catalytic dyad in various NBDs: Mg^2+/ATP-bound catalytic site conformation of wild-type MRP1–NBD1 (a), Na^+/ATP-bound MJ0796–E171Q inactive mutant pdb code 1l2t (b), nucleotide free wild-type MalK pdb code 1q1e (c), and ATP-bound MalK pdb code 1q12 (d).
  The above figures are reprinted by permission from Elsevier: J Mol Biol (2006, 359, 940-949) copyright 2006.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
22447242 M.Hohl, C.Briand, M.G.Grütter, and M.A.Seeger (2012).
Crystal structure of a heterodimeric ABC transporter in its inward-facing conformation.
  Nat Struct Mol Biol, 19, 395-402.
PDB code: 3qf4
21315686 R.Yang, Y.X.Hou, C.A.Campbell, K.Palaniyandi, Q.Zhao, A.J.Bordner, and X.B.Chang (2011).
Glutamine residues in Q-loops of multidrug resistance protein MRP1 contribute to ATP binding via interaction with metal cofactor.
  Biochim Biophys Acta, 1808, 1790-1796.  
19603203 C.E.Cassidy, and W.N.Setzer (2010).
Cancer-relevant biochemical targets of cytotoxic Lonchocarpus flavonoids: a molecular docking analysis.
  J Mol Model, 16, 311-326.  
20799350 L.Kelly, H.Fukushima, R.Karchin, J.M.Gow, L.W.Chinn, U.Pieper, M.R.Segal, D.L.Kroetz, and A.Sali (2010).
Functional hot spots in human ATP-binding cassette transporter nucleotide binding domains.
  Protein Sci, 19, 2110-2121.  
20823549 M.Haffke, A.Menzel, Y.Carius, D.Jahn, and D.W.Heinz (2010).
Structures of the nucleotide-binding domain of the human ABCB6 transporter and its complexes with nucleotides.
  Acta Crystallogr D Biol Crystallogr, 66, 979-987.
PDB codes: 3nh6 3nh9 3nha 3nhb
20162627 O.Doppelt-Azeroual, F.Delfaud, F.Moriaud, and Brevern (2010).
Fast and automated functional classification with MED-SuMo: an application on purine-binding proteins.
  Protein Sci, 19, 847-867.  
18957373 D.Muallem, and P.Vergani (2009).
Review. ATP hydrolysis-driven gating in cystic fibrosis transmembrane conductance regulator.
  Philos Trans R Soc Lond B Biol Sci, 364, 247-255.  
18990670 J.Aittoniemi, C.Fotinou, T.J.Craig, Wet, P.Proks, and F.M.Ashcroft (2009).
Review. SUR1: a unique ATP-binding cassette protein that functions as an ion channel regulator.
  Philos Trans R Soc Lond B Biol Sci, 364, 257-267.  
19421845 P.Matsson, J.M.Pedersen, U.Norinder, C.A.Bergström, and P.Artursson (2009).
Identification of novel specific and general inhibitors of the three major human ATP-binding cassette transporters P-gp, BCRP and MRP2 among registered drugs.
  Pharm Res, 26, 1816-1831.  
19265398 S.Balaz (2009).
Modeling kinetics of subcellular disposition of chemicals.
  Chem Rev, 109, 1793-1899.  
19453273 U.A.Hellmich, and C.Glaubitz (2009).
NMR and EPR studies of membrane transporters.
  Biol Chem, 390, 815-834.  
19544044 V.Kos, and R.C.Ford (2009).
The ATP-binding cassette family: a structural perspective.
  Cell Mol Life Sci, 66, 3111-3126.  
19691360 Y.X.Hou, C.Z.Li, K.Palaniyandi, P.M.Magtibay, L.Homolya, B.Sarkadi, and X.B.Chang (2009).
Effects of putative catalytic base mutation E211Q on ABCG2-mediated methotrexate transport.
  Biochemistry, 48, 9122-9131.  
18618153 N.R.Tawari, S.Bag, and M.S.Degani (2008).
Pharmacophore mapping of a series of pyrrolopyrimidines, indolopyrimidines and their congeners as multidrug-resistance-associated protein (MRP1) modulators.
  J Mol Model, 14, 911-921.  
18088596 R.Yang, R.Scavetta, and X.B.Chang (2008).
The hydroxyl group of S685 in Walker A motif and the carboxyl group of D792 in Walker B motif of NBD1 play a crucial role for multidrug resistance protein folding and function.
  Biochim Biophys Acta, 1778, 454-465.  
17187755 R.Yang, and X.B.Chang (2007).
Hydrogen-bond formation of the residue in H-loop of the nucleotide binding domain 2 with the ATP in this site and/or other residues of multidrug resistance protein MRP1 plays a crucial role during ATP-dependent solute transport.
  Biochim Biophys Acta, 1768, 324-335.  
17295059 X.B.Chang (2007).
A molecular understanding of ATP-dependent solute transport by multidrug resistance-associated protein MRP1.
  Cancer Metastasis Rev, 26, 15-37.  
16864587 R.Ernst, J.Koch, C.Horn, R.Tampé, and L.Schmitt (2006).
Engineering ATPase activity in the isolated ABC cassette of human TAP1.
  J Biol Chem, 281, 27471-27480.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB code is shown on the right.