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PDBsum entry 1idr
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Oxygen storage/transport PDB id
1idr

 

 

 

 

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Contents
Protein chains
127 a.a. *
Ligands
PO4 ×3
HEM-OXY ×2
Waters ×228
* Residue conservation analysis
PDB id:
1idr
Name: Oxygen storage/transport
Title: Crystal structure of the truncated-hemoglobin-n from mycobacterium tuberculosis
Structure: Hemoglobin hbn. Chain: a, b. Engineered: yes
Source: Mycobacterium tuberculosis. Organism_taxid: 1773. Expressed in: escherichia coli. Expression_system_taxid: 562
Resolution:
1.90Å     R-factor:   0.192     R-free:   0.250
Authors: M.Milani,A.Pesce,P.Ascenzi,M.Guertin,M.Bolognesi
Key ref:
M.Milani et al. (2001). Mycobacterium tuberculosis hemoglobin N displays a protein tunnel suited for O2 diffusion to the heme. EMBO J, 20, 3902-3909. PubMed id: 11483493 DOI: 10.1093/emboj/20.15.3902
Date:
05-Apr-01     Release date:   22-Aug-01    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P9WN25  (TRHBN_MYCTU) -  Group 1 truncated hemoglobin GlbN from Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)
Seq:
Struc: 		136 a.a.
127 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.?
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]

 

 
DOI no: 10.1093/emboj/20.15.3902 EMBO J 20:3902-3909 (2001)
PubMed id: 11483493  
 
 
Mycobacterium tuberculosis hemoglobin N displays a protein tunnel suited for O2 diffusion to the heme.
M.Milani, A.Pesce, Y.Ouellet, P.Ascenzi, M.Guertin, M.Bolognesi.
 
  ABSTRACT  
 
Macrophage-generated oxygen- and nitrogen-reactive species control the development of Mycobacterium tuberculosis infection in the host. Mycobacterium tuberculosis 'truncated hemoglobin' N (trHbN) has been related to nitric oxide (NO) detoxification, in response to macrophage nitrosative stress, during the bacterium latent infection stage. The three-dimensional structure of oxygenated trHbN, solved at 1.9 A resolution, displays the two-over-two alpha-helical sandwich fold recently characterized in two homologous truncated hemoglobins, featuring an extra N-terminal alpha-helix and homodimeric assembly. In the absence of a polar distal E7 residue, the O2 heme ligand is stabilized by two hydrogen bonds to TyrB10(33). Strikingly, ligand diffusion to the heme in trHbN may occur via an apolar tunnel/cavity system extending for approximately 28 A through the protein matrix, connecting the heme distal cavity to two distinct protein surface sites. This unique structural feature appears to be conserved in several homologous truncated hemoglobins. It is proposed that in trHbN, heme Fe/O2 stereochemistry and the protein matrix tunnel may promote O2/NO chemistry in vivo, as a M.tuberculosis defense mechanism against macrophage nitrosative stress.
 
  Selected figure(s)  
 
Figure 2.
Figure 2 (A) Ribbon stereo view of trHbN (A-chain), including the heme group, the O[2] molecule (red) and some of the residues deemed relevant for trHb fold stability or for trHbN functionality. Locations of the invariant Gly-based motifs are highlighted in yellow. Secondary structure elements are labeled in black. All figures were drawn with MOLSCRIPT (Kraulis, 1991) and Raster3D (Merritt and Bacon, 1997). (B) A stereo view of the main distal and proximal site residues in trHbN, together with the O[2] molecule (in red), the heme group, the one-turn F-helix and segments of helices B, E and H. 		Figure 3.
Figure 3 (A) Stereo view of the protein matrix tunnel observed in trHbN. The tunnel surface, defined by a 1.4 Å radius probe, is portrayed in light blue. The distal site cavity surface is calculated and displayed in the absence of the O[2] molecule, which is, however, shown in red for reference. Residue PheE15(62), causing the main restriction to the tunnel diameter, is shown in black; the other residues lining the tunnel walls are portrayed in gray. The estimated tunnel volume is 330 Å3. (B) For comparison, C-trHb protein backbone (blue) is portrayed in the same orientation as in Figure 3A, together with the protein matrix tunnel surface (orange), calculated as described above. Capital letters identify selected -helices in the trHb fold. Both trHbs are shown approximately in the same orientation and scale.
 
  The above figures are reprinted from an Open Access publication published by Macmillan Publishers Ltd: EMBO J (2001, 20, 3902-3909) copyright 2001.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21298302 F.P.Nicoletti, M.K.Thompson, S.Franzen, and G.Smulevich (2011).
Degradation of sulfide by dehaloperoxidase-hemoglobin from Amphitrite ornata.
  J Biol Inorg Chem, 16, 611-619.  
21298303 J.Igarashi, K.Kobayashi, and A.Matsuoka (2011).
A hydrogen-bonding network formed by the B10-E7-E11 residues of a truncated hemoglobin from Tetrahymena pyriformis is critical for stability of bound oxygen and nitric oxide detoxification.
  J Biol Inorg Chem, 16, 599-609.
PDB codes: 3aq5 3aq6 3aq7 3aq8 3aq9
21445853 M.S.Heroux, A.D.Mohan, and K.W.Olsen (2011).
Ligand migration in the truncated hemoglobin of Mycobacterium tuberculosis.
  IUBMB Life, 63, 214-220.  
19899166 L.Boechi, P.A.Mañez, F.J.Luque, M.A.Marti, and D.A.Estrin (2010).
Unraveling the molecular basis for ligand binding in truncated hemoglobins: the trHbO Bacillus subtilis case.
  Proteins, 78, 962-970.  
20179337 T.Kuwada, T.Hasegawa, T.Takagi, I.Sato, and F.Shishikura (2010).
pH-dependent structural changes in haemoglobin component V from the midge larva Propsilocerus akamusi (Orthocladiinae, Diptera).
  Acta Crystallogr D Biol Crystallogr, 66, 258-267.
PDB codes: 2zwj 3a5a 3a5b 3a5g 3a9m
19329431 A.Lama, S.Pawaria, A.Bidon-Chanal, A.Anand, J.L.Gelpí, S.Arya, M.Martí, D.A.Estrin, F.J.Luque, and K.L.Dikshit (2009).
Role of Pre-A motif in nitric oxide scavenging by truncated hemoglobin, HbN, of Mycobacterium tuberculosis.
  J Biol Chem, 284, 14457-14468.  
19913484 J.E.Knapp, R.Pahl, J.Cohen, J.C.Nichols, K.Schulten, Q.H.Gibson, V.Srajer, and W.E.Royer (2009).
Ligand migration and cavities within Scapharca Dimeric HbI: studies by time-resolved crystallo-graphy, Xe binding, and computational analysis.
  Structure, 17, 1494-1504.
PDB codes: 3g46 3g4q 3g4r 3g4u 3g4v 3g4w 3g4y 3g52 3g53
19948126 R.Daigle, J.A.Rousseau, M.Guertin, and P.Lagüe (2009).
Theoretical investigations of nitric oxide channeling in Mycobacterium tuberculosis truncated hemoglobin N.
  Biophys J, 97, 2967-2977.  
19003999 R.Daigle, M.Guertin, and P.Lagüe (2009).
Structural characterization of the tunnels of Mycobacterium tuberculosis truncated hemoglobin N from molecular dynamics simulations.
  Proteins, 75, 735-747.  
19653642 R.Tran, E.M.Boon, M.A.Marletta, and R.A.Mathies (2009).
Resonance Raman spectra of an O2-binding H-NOX domain reveal heme relaxation upon mutation.
  Biochemistry, 48, 8568-8577.  
19289037 S.Mishra, and M.Meuwly (2009).
Nitric oxide dynamics in truncated hemoglobin: docking sites, migration pathways, and vibrational spectroscopy from molecular dynamics simulations.
  Biophys J, 96, 2105-2118.  
19751675 T.Moschetti, U.Mueller, J.Schulze, M.Brunori, and B.Vallone (2009).
The structure of neuroglobin at high Xe and Kr pressure reveals partial conservation of globin internal cavities.
  Biophys J, 97, 1700-1708.  
18190529 A.Bolli, C.Ciaccio, M.Coletta, M.Nardini, M.Bolognesi, A.Pesce, M.Guertin, P.Visca, and P.Ascenzi (2008).
Ferrous Campylobacter jejuni truncated hemoglobin P displays an extremely high reactivity for cyanide - a comparative study.
  FEBS J, 275, 633-645.  
18548291 G.Razzera, J.Vernal, D.Baruh, V.I.Serpa, C.Tavares, F.Lara, E.M.Souza, F.O.Pedrosa, F.C.Almeida, H.Terenzi, and A.P.Valente (2008).
Spectroscopic characterization of a truncated hemoglobin from the nitrogen-fixing bacterium Herbaspirillum seropedicae.
  J Biol Inorg Chem, 13, 1085-1096.  
18203714 J.A.Gavira, A.Camara-Artigas, W.De Jesús-Bonilla, J.López-Garriga, A.Lewis, R.Pietri, S.R.Yeh, C.L.Cadilla, and J.M.García-Ruiz (2008).
Structure and ligand selection of hemoglobin II from Lucina pectinata.
  J Biol Chem, 283, 9414-9423.
PDB code: 2olp
18820019 J.Niemann, and L.S.Tisa (2008).
Nitric oxide and oxygen regulate truncated hemoglobin gene expression in Frankia strain CcI3.
  J Bacteriol, 190, 7864-7867.  
18433052 L.Boechi, M.A.Martí, M.Milani, M.Bolognesi, F.J.Luque, and D.A.Estrin (2008).
Structural determinants of ligand migration in Mycobacterium tuberculosis truncated hemoglobin O.
  Proteins, 73, 372-379.  
18840607 M.D.Salter, K.Nienhaus, G.U.Nienhaus, S.Dewilde, L.Moens, A.Pesce, M.Nardini, M.Bolognesi, and J.S.Olson (2008).
The Apolar Channel in Cerebratulus lacteus Hemoglobin Is the Route for O2 Entry and Exit.
  J Biol Chem, 283, 35689-35702.
PDB codes: 2vyy 2vyz
17803238 O.Carrillo, and M.Orozco (2008).
GRID-MD-A tool for massive simulation of protein channels.
  Proteins, 70, 892-899.  
18676995 Y.H.Ouellet, R.Daigle, P.Lagüe, D.Dantsker, M.Milani, M.Bolognesi, J.M.Friedman, and M.Guertin (2008).
Ligand Binding to Truncated Hemoglobin N from Mycobacterium tuberculosis Is Strongly Modulated by the Interplay between the Distal Heme Pocket Residues and Internal Water.
  J Biol Chem, 283, 27270-27278.  
17339325 C.Lu, T.Egawa, L.M.Wainwright, R.K.Poole, and S.R.Yeh (2007).
Structural and functional properties of a truncated hemoglobin from a food-borne pathogen Campylobacter jejuni.
  J Biol Chem, 282, 13627-13636.  
17318598 M.A.Carrondo, I.Bento, P.M.Matias, and P.F.Lindley (2007).
Crystallographic evidence for dioxygen interactions with iron proteins.
  J Biol Inorg Chem, 12, 429-442.  
17531406 P.Deng, K.Nienhaus, P.Palladino, J.S.Olson, G.Blouin, L.Moens, S.Dewilde, E.Geuens, and G.U.Nienhaus (2007).
Transient ligand docking sites in Cerebratulus lacteus mini-hemoglobin.
  Gene, 398, 208-223.  
17289341 S.Pawaria, G.Rajamohan, V.Gambhir, A.Lama, G.C.Varshney, and K.L.Dikshit (2007).
Intracellular growth and survival of Salmonella enterica serovar Typhimurium carrying truncated hemoglobins of Mycobacterium tuberculosis.
  Microb Pathog, 42, 119-128.  
16688782 A.Bidon-Chanal, M.A.Martí, A.Crespo, M.Milani, M.Orozco, M.Bolognesi, F.J.Luque, and D.A.Estrin (2006).
Ligand-induced dynamical regulation of NO conversion in Mycobacterium tuberculosis truncated hemoglobin-N.
  Proteins, 64, 457-464.  
16474979 D.A.Vuletich, and J.T.Lecomte (2006).
A phylogenetic and structural analysis of truncated hemoglobins.
  J Mol Evol, 62, 196-210.  
17149482 D.E.Bikiel, L.Boechi, L.Capece, A.Crespo, P.M.De Biase, S.Di Lella, M.C.González Lebrero, M.A.Martí, A.D.Nadra, L.L.Perissinotti, D.A.Scherlis, and D.A.Estrin (2006).
Modeling heme proteins using atomistic simulations.
  Phys Chem Chem Phys, 8, 5611-5628.  
16586113 F.A.Walker (2006).
The heme environment of mouse neuroglobin: histidine imidazole plane orientations obtained from solution NMR and EPR spectroscopy as compared with X-ray crystallography.
  J Biol Inorg Chem, 11, 391-397.  
16681372 L.M.Wainwright, Y.Wang, S.F.Park, S.R.Yeh, and R.K.Poole (2006).
Purification and spectroscopic characterization of Ctb, a group III truncated hemoglobin implicated in oxygen metabolism in the food-borne pathogen Campylobacter jejuni.
  Biochemistry, 45, 6003-6011.  
16315240 L.Marsella (2006).
Modeling truncated hemoglobin vibrational dynamics.
  Proteins, 62, 173-182.  
17023416 M.Nardini, A.Pesce, M.Labarre, C.Richard, A.Bolli, P.Ascenzi, M.Guertin, and M.Bolognesi (2006).
Structural determinants in the group III truncated hemoglobin from Campylobacter jejuni.
  J Biol Chem, 281, 37803-37812.
PDB code: 2ig3
16600051 S.N.Vinogradov, D.Hoogewijs, X.Bailly, R.Arredondo-Peter, J.Gough, S.Dewilde, L.Moens, and J.R.Vanfleteren (2006).
A phylogenomic profile of globins.
  BMC Evol Biol, 6, 31.  
15917230 D.de Sanctis, S.Dewilde, C.Vonrhein, A.Pesce, L.Moens, P.Ascenzi, T.Hankeln, T.Burmester, M.Ponassi, M.Nardini, and M.Bolognesi (2005).
Bishistidyl heme hexacoordination, a key structural property in Drosophila melanogaster hemoglobin.
  J Biol Chem, 280, 27222-27229.
PDB code: 2bk9
15922591 J.T.Lecomte, D.A.Vuletich, and A.M.Lesk (2005).
Structural divergence and distant relationships in proteins: evolution of the globins.
  Curr Opin Struct Biol, 15, 290-301.  
15590662 L.Giangiacomo, A.Ilari, A.Boffi, V.Morea, and E.Chiancone (2005).
The truncated oxygen-avid hemoglobin from Bacillus subtilis: X-ray structure and ligand binding properties.
  J Biol Chem, 280, 9192-9202.
PDB code: 1ux8
16061809 S.N.Vinogradov, D.Hoogewijs, X.Bailly, R.Arredondo-Peter, M.Guertin, J.Gough, S.Dewilde, L.Moens, and J.R.Vanfleteren (2005).
Three globin lineages belonging to two structural classes in genomes from the three kingdoms of life.
  Proc Natl Acad Sci U S A, 102, 11385-11389.  
15162488 B.Vallone, K.Nienhaus, M.Brunori, and G.U.Nienhaus (2004).
The structure of murine neuroglobin: Novel pathways for ligand migration and binding.
  Proteins, 56, 85-92.
PDB code: 1q1f
15234986 D.Dantsker, U.Samuni, Y.Ouellet, B.A.Wittenberg, J.B.Wittenberg, M.Milani, M.Bolognesi, M.Guertin, and J.M.Friedman (2004).
Viscosity-dependent relaxation significantly modulates the kinetics of CO recombination in the truncated hemoglobin TrHbN from Mycobacterium tuberculosis.
  J Biol Chem, 279, 38844-38853.  
14736872 J.A.Hoy, S.Kundu, J.T.Trent, S.Ramaswamy, and M.S.Hargrove (2004).
The crystal structure of Synechocystis hemoglobin with a covalent heme linkage.
  J Biol Chem, 279, 16535-16542.
PDB code: 1rtx
15016811 M.Milani, A.Pesce, Y.Ouellet, S.Dewilde, J.Friedman, P.Ascenzi, M.Guertin, and M.Bolognesi (2004).
Heme-ligand tunneling in group I truncated hemoglobins.
  J Biol Chem, 279, 21520-21525.
PDB codes: 1s56 1s61 1uvx 1uvy
14728676 S.Ghisla, and C.Thorpe (2004).
Acyl-CoA dehydrogenases. A mechanistic overview.
  Eur J Biochem, 271, 494-508.  
15096613 T.A.Freitas, S.Hou, E.M.Dioum, J.A.Saito, J.Newhouse, G.Gonzalez, M.A.Gilles-Gonzalez, and M.Alam (2004).
Ancestral hemoglobins in Archaea.
  Proc Natl Acad Sci U S A, 101, 6675-6680.  
14688246 T.K.Das, U.Samuni, Y.Lin, D.E.Goldberg, D.L.Rousseau, and J.M.Friedman (2004).
Distal heme pocket conformers of carbonmonoxy derivatives of Ascaris hemoglobin: evidence of conformational trapping in porous sol-gel matrices.
  J Biol Chem, 279, 10433-10441.  
14550944 A.D.Frey, and P.T.Kallio (2003).
Bacterial hemoglobins and flavohemoglobins: versatile proteins and their impact on microbiology and biotechnology.
  FEMS Microbiol Rev, 27, 525-545.  
12962627 A.Pesce, S.Dewilde, M.Nardini, L.Moens, P.Ascenzi, T.Hankeln, T.Burmester, and M.Bolognesi (2003).
Human brain neuroglobin structure reveals a distinct mode of controlling oxygen affinity.
  Structure, 11, 1087-1095.
PDB code: 1oj6
12915092 M.Bellinzoni, and G.Riccardi (2003).
Techniques and applications: The heterologous expression of Mycobacterium tuberculosis genes is an uphill road.
  Trends Microbiol, 11, 351-358.  
12719529 M.Milani, P.Y.Savard, H.Ouellet, P.Ascenzi, M.Guertin, and M.Bolognesi (2003).
A TyrCD1/TrpG8 hydrogen bond network and a TyrB10TyrCD1 covalent link shape the heme distal site of Mycobacterium tuberculosis hemoglobin O.
  Proc Natl Acad Sci U S A, 100, 5766-5771.
PDB code: 1ngk
12736253 U.Samuni, D.Dantsker, A.Ray, J.B.Wittenberg, B.A.Wittenberg, S.Dewilde, L.Moens, Y.Ouellet, M.Guertin, and J.M.Friedman (2003).
Kinetic modulation in carbonmonoxy derivatives of truncated hemoglobins: the role of distal heme pocket residues and extended apolar tunnel.
  J Biol Chem, 278, 27241-27250.  
12823541 W.Du, Z.Xia, S.Dewilde, L.Moens, and G.N.La Mar (2003).
1H NMR study of the molecular structure and magnetic properties of the active site for the cyanomet complex of O2-avid hemoglobin from the trematode Paramphistomum epiclitum.
  Eur J Biochem, 270, 2707-2720.  
12015154 A.Pesce, M.Nardini, S.Dewilde, E.Geuens, K.Yamauchi, P.Ascenzi, A.F.Riggs, L.Moens, and M.Bolognesi (2002).
The 109 residue nerve tissue minihemoglobin from Cerebratulus lacteus highlights striking structural plasticity of the alpha-helical globin fold.
  Structure, 10, 725-735.
PDB code: 1kr7
12351835 A.Pesce, M.Nardini, S.Dewilde, P.Ascenzi, T.Burmester, T.Hankeln, L.Moens, and M.Bolognesi (2002).
Human neuroglobin: crystals and preliminary X-ray diffraction analysis.
  Acta Crystallogr D Biol Crystallogr, 58, 1848-1850.  
11959913 H.Ouellet, Y.Ouellet, C.Richard, M.Labarre, B.Wittenberg, J.Wittenberg, and M.Guertin (2002).
Truncated hemoglobin HbN protects Mycobacterium bovis from nitric oxide.
  Proc Natl Acad Sci U S A, 99, 5902-5907.  
11900532 M.Mukai, P.Y.Savard, H.Ouellet, M.Guertin, and S.R.Yeh (2002).
Unique ligand-protein interactions in a new truncated hemoglobin from Mycobacterium tuberculosis.
  Biochemistry, 41, 3897-3905.  
12207698 R.Pathania, N.K.Navani, A.M.Gardner, P.R.Gardner, and K.L.Dikshit (2002).
Nitric oxide scavenging and detoxification by the Mycobacterium tuberculosis haemoglobin, HbN in Escherichia coli.
  Mol Microbiol, 45, 1303-1314.  
11796724 R.Pathania, N.K.Navani, G.Rajamohan, and K.L.Dikshit (2002).
Mycobacterium tuberculosis hemoglobin HbO associates with membranes and stimulates cellular respiration of recombinant Escherichia coli.
  J Biol Chem, 277, 15293-15302.  
11717510 A.Pesce, M.Nardini, S.Dewilde, P.Ascenzi, A.F.Riggs, K.Yamauchi, E.Geuens, L.Moens, and M.Bolognesi (2001).
Crystallization and preliminary X-ray analysis of neural haemoglobin from the nemertean worm Cerebratulus lacteus.
  Acta Crystallogr D Biol Crystallogr, 57, 1897-1899.  
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 codes are shown on the right.

 

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