spacer
spacer

PDBsum entry 9ilb

Go to PDB code: 
protein links
Signaling protein PDB id
9ilb
Jmol PyMol
Contents
Protein chain
153 a.a. *
Waters ×56
* Residue conservation analysis
PDB id:
9ilb
Name: Signaling protein
Title: Human interleukin-1 beta
Structure: Protein (human interleukin-1 beta). Chain: a. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562
Resolution:
2.28Å     R-factor:   0.157     R-free:   0.210
Authors: B.Yu,M.Blaber,A.M.Gronenborn,G.M.Clore,D.L.D.Caspar
Key ref:
B.Yu et al. (1999). Disordered water within a hydrophobic protein cavity visualized by x-ray crystallography. Proc Natl Acad Sci U S A, 96, 103-108. PubMed id: 9874779 DOI: 10.1073/pnas.96.1.103
Date:
22-Oct-98     Release date:   06-Jan-99    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P01584  (IL1B_HUMAN) -  Interleukin-1 beta
Seq:
Struc:
269 a.a.
153 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     extracellular region   2 terms 
  Biological process     immune response   2 terms 
  Biochemical function     cytokine activity     2 terms  

 

 
DOI no: 10.1073/pnas.96.1.103 Proc Natl Acad Sci U S A 96:103-108 (1999)
PubMed id: 9874779  
 
 
Disordered water within a hydrophobic protein cavity visualized by x-ray crystallography.
B.Yu, M.Blaber, A.M.Gronenborn, G.M.Clore, D.L.Caspar.
 
  ABSTRACT  
 
Water in the hydrophobic cavity of human interleukin 1beta, which was detected by NMR spectroscopy but was invisible by high resolution x-ray crystallography, has been mapped quantitatively by measurement and phasing of all of the low resolution x-ray diffraction data from a single crystal. Phases for the low resolution data were refined by iterative density modification of an initial flat solvent model outside the envelope of the atomic model. The refinement was restrained by the condition that the map of the difference between the electron density distribution in the full unit cell and that of the atomic model be flat within the envelope of the well ordered protein structure. Care was taken to avoid overfitting the diffraction data by maintaining phases for the high resolution data from the atomic model and by a resolution-dependent damping of the structure factor differences between data and model. The cavity region in the protein could accommodate up to four water molecules. The refined solvent difference map indicates that there are about two water molecules in the cavity region. This map is compatible with an atomic model of the water distribution refined by using XPLOR. About 70% of the time, there appears to be a water dimer in the central hydrophobic cavity, which is connected to the outside by two constricted channels occupied by single water molecules approximately 40% of the time on one side and approximately 10% on the other.
 
  Selected figure(s)  
 
Figure 1.
Fig. 1. R factors as a function of resolution: , refined protein structure in vacuum; ×, after first cycle of difference map refinement; , after 20 cycles of refinement. Definition of R factor for the nth cycle of refinement: = \sumh||||F(h)mod,n|| -||F(h)obs||||||F(h)obs|| F(h)[mod,n] is the structure factor of index hkl after the nth cycle of bulk solvent density modification, and F(h)[obs] is the observed value.
Figure 2.
Fig. 2. Difference map of the density distribution within the cavity region of the hIL-1 molecule that is not accounted for by the refined atomic model. (A) The difference electron density map within a sphere of 10-Å radius is displayed inside the C[ ]trace of an hIL-1 molecule viewed from the side containing the C terminus (center) and N terminus (top), with ball and stick representations of the cavity forming residues. The methyl groups of the aliphatic residues are drawn as large tan spheres, and the aromatic carbons are smaller, light blue spheres. Every tenth C[ ]atom is labeled, except 120, which is obscured behind the cavity density map. The red contours contain 70% of the total of 18 solvent electrons integrated in the cavity region, and the blue contours contain 50% of these electrons. (B and C) Stereopair images of the cavity solvent density within a sphere of 6-Å radius are viewed from the front (B) and back (C) of the orientation shown in A. The six leucine (L) one isoleucine (I), one valine (V), and four phenylalanine (F) residues forming the cavity are labeled. The green contours superimposed on the solvent difference map mark the envelope of the atomic model of the partially occupied water molecules in the cavity, refined with the protein model by XPLOR. This model, which contains 18.5 electrons, is contoured at the 70% level. The difference in shape of the experimental solvent difference map (red and blue) based on refinement of phases for the low resolution diffraction data and the XPLOR model of the cavity water (green) based on refinement of a single-conformer protein model may be caused by fluctuations in the cavity shape or, alternatively, to noise in diffraction data. The graphics were created with O (28), MOLSCRIPT (29), and RAYSHADE (30).
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
20665475 M.Bueno, N.A.Temiz, and C.J.Camacho (2010).
Novel modulation factor quantifies the role of water molecules in protein interactions.
  Proteins, 78, 3226-3234.  
20823553 T.D.Fenn, M.J.Schnieders, and A.T.Brunger (2010).
A smooth and differentiable bulk-solvent model for macromolecular diffraction.
  Acta Crystallogr D Biol Crystallogr, 66, 1024-1031.  
  19241368 B.W.Matthews, and L.Liu (2009).
A review about nothing: are apolar cavities in proteins really empty?
  Protein Sci, 18, 494-502.  
18246106 G.G.Dodson, D.P.Lane, and C.S.Verma (2008).
Molecular simulations of protein dynamics: new windows on mechanisms in biology.
  EMBO Rep, 9, 144-150.  
18092942 J.C.Rasaiah, S.Garde, and G.Hummer (2008).
Water in nonpolar confinement: from nanotubes to proteins and beyond.
  Annu Rev Phys Chem, 59, 713-740.  
18391405 J.L.Knight, Z.Zhou, E.Gallicchio, D.M.Himmel, R.A.Friesner, E.Arnold, and R.M.Levy (2008).
Exploring structural variability in X-ray crystallographic models using protein local optimization by torsion-angle sampling.
  Acta Crystallogr D Biol Crystallogr, 64, 383-396.  
18427121 J.Qvist, M.Davidovic, D.Hamelberg, and B.Halle (2008).
A dry ligand-binding cavity in a solvated protein.
  Proc Natl Acad Sci U S A, 105, 6296-6301.  
18780783 L.Liu, M.L.Quillin, and B.W.Matthews (2008).
Use of experimental crystallographic phases to examine the hydration of polar and nonpolar cavities in T4 lysozyme.
  Proc Natl Acad Sci U S A, 105, 14406-14411.
PDB code: 3dke
19005575 S.Sonavane, and P.Chakrabarti (2008).
Cavities and atomic packing in protein structures and interfaces.
  PLoS Comput Biol, 4, e1000188.  
17541801 J.Tatur, W.R.Hagen, and P.M.Matias (2007).
Crystal structure of the ferritin from the hyperthermophilic archaeal anaerobe Pyrococcus furiosus.
  J Biol Inorg Chem, 12, 615-630.
PDB codes: 2jd6 2jd7 2jd8
17385863 N.Choudhury, and B.M.Pettitt (2007).
The dewetting transition and the hydrophobic effect.
  J Am Chem Soc, 129, 4847-4852.  
17380484 S.Somani, C.P.Chng, and C.S.Verma (2007).
Hydration of a hydrophobic cavity and its functional role: a simulation study of human interleukin-1beta.
  Proteins, 67, 868-885.  
17397537 S.V.Rakhmanov, and V.J.Makeev (2007).
Atomic hydration potentials using a Monte Carlo Reference State (MCRS) for protein solvation modeling.
  BMC Struct Biol, 7, 19.  
17131430 V.Helms (2007).
Protein dynamics tightly connected to the dynamics of surrounding and internal water molecules.
  Chemphyschem, 8, 23-33.  
16877708 M.Bueno, L.A.Campos, J.Estrada, and J.Sancho (2006).
Energetics of aliphatic deletions in protein cores.
  Protein Sci, 15, 1858-1872.  
17179045 M.L.Quillin, P.T.Wingfield, and B.W.Matthews (2006).
Determination of solvent content in cavities in IL-1beta using experimentally phased electron density.
  Proc Natl Acad Sci U S A, 103, 19749-19753.
PDB code: 2nvh
17038664 P.Cioni (2006).
Role of protein cavities on unfolding volume change and on internal dynamics under pressure.
  Biophys J, 91, 3390-3396.  
16154088 M.A.Depristo, P.I.de Bakker, R.J.Johnson, and T.L.Blundell (2005).
Crystallographic refinement by knowledge-based exploration of complex energy landscapes.
  Structure, 13, 1311-1319.  
16269539 M.D.Collins, G.Hummer, M.L.Quillin, B.W.Matthews, and S.M.Gruner (2005).
Cooperative water filling of a nonpolar protein cavity observed by high-pressure crystallography and simulation.
  Proc Natl Acad Sci U S A, 102, 16668-16671.
PDB codes: 2b6w 2b6x 2b6y 2b6z 2b70 2b72 2b73 2b74 2b75 2oe4
16014708 M.Wikström, C.Ribacka, M.Molin, L.Laakkonen, M.Verkhovsky, and A.Puustinen (2005).
Gating of proton and water transfer in the respiratory enzyme cytochrome c oxidase.
  Proc Natl Acad Sci U S A, 102, 10478-10481.  
16035017 N.Desbiens, I.Demachy, A.H.Fuchs, H.Kirsch-Rodeschini, M.Soulard, and J.Patarin (2005).
Water condensation in hydrophobic nanopores.
  Angew Chem Int Ed Engl, 44, 5310-5313.  
15731388 S.Grudinin, G.Büldt, V.Gordeliy, and A.Baumgaertner (2005).
Water molecules and hydrogen-bonded networks in bacteriorhodopsin--molecular dynamics simulations of the ground state and the M-intermediate.
  Biophys J, 88, 3252-3261.  
14745295 J.R.Trudell, and R.A.Harris (2004).
Are sobriety and consciousness determined by water in protein cavities?
  Alcohol Clin Exp Res, 28, 1-3.  
15130475 M.A.DePristo, P.I.de Bakker, and T.L.Blundell (2004).
Heterogeneity and inaccuracy in protein structures solved by X-ray crystallography.
  Structure, 12, 831-838.  
15382229 M.J.Bernett, T.Somasundaram, and M.Blaber (2004).
An atomic resolution structure for human fibroblast growth factor 1.
  Proteins, 57, 626-634.
PDB code: 1rg8
15572444 S.Vaitheeswaran, H.Yin, J.C.Rasaiah, and G.Hummer (2004).
Water clusters in nonpolar cavities.
  Proc Natl Acad Sci U S A, 101, 17002-17005.  
14640679 A.Maeda, J.Herzfeld, M.Belenky, R.Needleman, R.B.Gennis, S.P.Balashov, and T.G.Ebrey (2003).
Water-mediated hydrogen-bonded network on the cytoplasmic side of the Schiff base of the L photointermediate of bacteriorhodopsin.
  Biochemistry, 42, 14122-14129.  
14501109 A.S.Soares, D.L.Caspar, E.Weckert, A.Héroux, K.Hölzer, K.Schroer, J.Zellner, D.Schneider, W.Nolan, and R.M.Sweet (2003).
Three-beam interference is a sensitive measure of the efficacy of macromolecular refinement techniques.
  Acta Crystallogr D Biol Crystallogr, 59, 1716-1724.  
12829463 F.Dong, M.Vijayakumar, and H.X.Zhou (2003).
Comparison of calculation and experiment implicates significant electrostatic contributions to the binding stability of barnase and barstar.
  Biophys J, 85, 49-60.  
12554939 M.G.Rudolph, M.S.Kelker, T.R.Schneider, T.O.Yeates, V.Oseroff, D.K.Heidary, P.A.Jennings, and I.A.Wilson (2003).
Use of multiple anomalous dispersion to phase highly merohedrally twinned crystals of interleukin-1beta.
  Acta Crystallogr D Biol Crystallogr, 59, 290-298.
PDB code: 1l2h
12829464 W.Guo, S.Lampoudi, and J.E.Shea (2003).
Posttransition state desolvation of the hydrophobic core of the src-SH3 protein domain.
  Biophys J, 85, 61-69.  
12001232 D.Bakowies, and W.F.Van Gunsteren (2002).
Water in protein cavities: A procedure to identify internal water and exchange pathways and application to fatty acid-binding protein.
  Proteins, 47, 534-545.  
11908503 S.Yoshioki (2002).
Dynamics of a protein and water molecules surrounding the protein: hydrogen-bonding between vibrating water molecules and a fluctuating protein.
  J Comput Chem, 23, 402-413.  
11420436 V.V.Loladze, D.N.Ermolenko, and G.I.Makhatadze (2001).
Heat capacity changes upon burial of polar and nonpolar groups in proteins.
  Protein Sci, 10, 1343-1352.  
10713987 A.E.García, and G.Hummer (2000).
Water penetration and escape in proteins.
  Proteins, 38, 261-272.  
11015216 G.S.Ratnaparkhi, and R.Varadarajan (2000).
Thermodynamic and structural studies of cavity formation in proteins suggest that loss of packing interactions rather than the hydrophobic effect dominates the observed energetics.
  Biochemistry, 39, 12365-12374.
PDB codes: 1d5d 1d5e 1d5h
10545357 D.B.Williams, and M.H.Akabas (1999).
gamma-aminobutyric acid increases the water accessibility of M3 membrane-spanning segment residues in gamma-aminobutyric acid type A receptors
  Biophys J, 77, 2563-2574.  
10517869 P.Csermely (1999).
Chaperone-percolator model: a possible molecular mechanism of Anfinsen-cage-type chaperones.
  Bioessays, 21, 959-965.  
10512824 S.Channareddy, and N.Janes (1999).
Direct determination of hydration in the interdigitated and ripple phases of dihexadecylphosphatidylcholine: hydration of a hydrophobic cavity at the membrane/water interface.
  Biophys J, 77, 2046-2050.  
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.

 

spacer

spacer