spacer
spacer

PDBsum entry 1teu

Go to PDB code: 
protein metals links
Lyase PDB id
1teu
Jmol
Contents
Protein chain
258 a.a. *
Metals
_ZN
Waters ×114
* Residue conservation analysis
PDB id:
1teu
Name: Lyase
Title: Effect of shuttle location and ph environment on h+ transfer in human carbonic anhydrase ii
Structure: Carbonic anhydrase ii. Chain: x. Synonym: carbonate dehydratase ii, ca-ii, carbonic anhydrasE C. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: ca2. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.
Resolution:
2.00Å     R-factor:   0.134     R-free:   0.175
Authors: Z.Fisher,J.A.Hernandez Prada,C.K.Tu,D.Duda,C.Yoshioka,H.An, L.Govindasamy,D.N.Silverman,R.Mckenna
Key ref:
Z.Fisher et al. (2005). Structural and kinetic characterization of active-site histidine as a proton shuttle in catalysis by human carbonic anhydrase II. Biochemistry, 44, 1097-1105. PubMed id: 15667203 DOI: 10.1021/bi0480279
Date:
25-May-04     Release date:   25-Jan-05    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P00918  (CAH2_HUMAN) -  Carbonic anhydrase 2
Seq:
Struc:
260 a.a.
258 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.4.2.1.1  - Carbonate dehydratase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: H2CO3 = CO2 + H2O
H(2)CO(3)
= CO(2)
+ H(2)O
      Cofactor: Zn(2+)
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     extracellular space   11 terms 
  Biological process     angiotensin-mediated signaling pathway   21 terms 
  Biochemical function     protein binding     5 terms  

 

 
    Added reference    
 
 
DOI no: 10.1021/bi0480279 Biochemistry 44:1097-1105 (2005)
PubMed id: 15667203  
 
 
Structural and kinetic characterization of active-site histidine as a proton shuttle in catalysis by human carbonic anhydrase II.
Z.Fisher, J.A.Hernandez Prada, C.Tu, D.Duda, C.Yoshioka, H.An, L.Govindasamy, D.N.Silverman, R.McKenna.
 
  ABSTRACT  
 
In the catalysis of the hydration of carbon dioxide and dehydration of bicarbonate by human carbonic anhydrase II (HCA II), a histidine residue (His64) shuttles protons between the zinc-bound solvent molecule and the bulk solution. To evaluate the effect of the position of the shuttle histidine and pH on proton shuttling, we have examined the catalysis and crystal structures of wild-type HCA II and two double mutants: H64A/N62H and H64A/N67H HCA II. His62 and His67 both have their side chains extending into the active-site cavity with distances from the zinc approximately equivalent to that of His64. Crystal structures were determined at pH 5.1-10.0, and the catalysis of the exchange of (18)O between CO(2) and water was assessed by mass spectrometry. Efficient proton shuttle exceeding a rate of 10(5) s(-)(1) was observed for histidine at positions 64 and 67; in contrast, relatively inefficient proton transfer at a rate near 10(3) s(-)(1) was observed for His62. The observation, in the crystal structures, of a completed hydrogen-bonded water chain between the histidine shuttle residue and the zinc-bound solvent does not appear to be required for efficient proton transfer. The data suggest that the number of intervening water molecules between the donor and acceptor supporting efficient proton transfer in HCA II is important, and furthermore suggest that a water bridge consisting of two intervening water molecules is consistent with efficient proton transfer.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
19765680 C.M.Maupin, and G.A.Voth (2010).
Proton transport in carbonic anhydrase: Insights from molecular simulation.
  Biochim Biophys Acta, 1804, 332-341.  
19679199 R.L.Mikulski, and D.N.Silverman (2010).
Proton transfer in catalysis and the role of proton shuttles in carbonic anhydrase.
  Biochim Biophys Acta, 1804, 422-426.  
20023030 S.A.Zimmerman, J.F.Tomb, and J.G.Ferry (2010).
Characterization of CamH from Methanosarcina thermophila, founding member of a subclass of the {gamma} class of carbonic anhydrases.
  J Bacteriol, 192, 1353-1360.  
20025241 S.Z.Fisher, A.Y.Kovalevsky, J.F.Domsic, M.Mustyakimov, R.McKenna, D.N.Silverman, and P.A.Langan (2010).
Neutron structure of human carbonic anhydrase II: implications for proton transfer.
  Biochemistry, 49, 415-421.
PDB code: 3kkx
19170619 C.Genis, K.H.Sippel, N.Case, W.Cao, B.S.Avvaru, L.J.Tartaglia, L.Govindasamy, C.Tu, M.Agbandje-McKenna, D.N.Silverman, C.J.Rosser, and R.McKenna (2009).
Design of a carbonic anhydrase IX active-site mimic to screen inhibitors for possible anticancer properties.
  Biochemistry, 48, 1322-1331.
PDB codes: 3d8w 3d9z 3daz 3dbu 3dc3 3dc9 3dcc 3dcs 3dcw 3dd0
19634894 C.M.Maupin, J.Zheng, C.Tu, R.McKenna, D.N.Silverman, and G.A.Voth (2009).
Effect of active-site mutation at Asn67 on the proton transfer mechanism of human carbonic anhydrase II.
  Biochemistry, 48, 7996-8005.  
19438233 C.M.Maupin, R.McKenna, D.N.Silverman, and G.A.Voth (2009).
Elucidation of the proton transport mechanism in human carbonic anhydrase II.
  J Am Chem Soc, 131, 7598-7608.  
  19407386 S.Z.Fisher, A.Y.Kovalevsky, J.F.Domsic, M.Mustyakimov, D.N.Silverman, R.McKenna, and P.Langan (2009).
Preliminary joint neutron and X-ray crystallographic study of human carbonic anhydrase II.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 65, 495-498.  
19015272 V.B.Bergo, O.A.Sineshchekov, J.M.Kralj, R.Partha, E.N.Spudich, K.J.Rothschild, and J.L.Spudich (2009).
His-75 in Proteorhodopsin, a Novel Component in Light-driven Proton Translocation by Primary Pumps.
  J Biol Chem, 284, 2836-2843.  
18671353 C.M.Maupin, M.G.Saunders, I.F.Thorpe, R.McKenna, D.N.Silverman, and G.A.Voth (2008).
Origins of enhanced proton transport in the Y7F mutant of human carbonic anhydrase II.
  J Am Chem Soc, 130, 11399-11408.  
18589895 J.Seravalli, and S.W.Ragsdale (2008).
13C NMR characterization of an exchange reaction between CO and CO2 catalyzed by carbon monoxide dehydrogenase.
  Biochemistry, 47, 6770-6781.  
18942852 J.Zheng, B.S.Avvaru, C.Tu, R.McKenna, and D.N.Silverman (2008).
Role of hydrophilic residues in proton transfer during catalysis by human carbonic anhydrase II.
  Biochemistry, 47, 12028-12036.
PDB codes: 3dv7 3dvb 3dvc 3dvd
18599462 N.Shah, D.A.Kuntz, and D.R.Rose (2008).
Golgi alpha-mannosidase II cleaves two sugars sequentially in the same catalytic site.
  Proc Natl Acad Sci U S A, 105, 9570-9575.
PDB codes: 3cv5 3czn 3czs
18335973 V.M.Krishnamurthy, G.K.Kaufman, A.R.Urbach, I.Gitlin, K.L.Gudiksen, D.B.Weibel, and G.M.Whitesides (2008).
Carbonic anhydrase as a model for biophysical and physical-organic studies of proteins and protein-ligand binding.
  Chem Rev, 108, 946.  
17319695 C.M.Maupin, and G.A.Voth (2007).
Preferred orientations of His64 in human carbonic anhydrase II.
  Biochemistry, 46, 2938-2947.  
17071654 D.Bhatt, S.Z.Fisher, C.Tu, R.McKenna, and D.N.Silverman (2007).
Location of binding sites in small molecule rescue of human carbonic anhydrase II.
  Biophys J, 92, 562-570.
PDB codes: 2fnk 2fnm 2fnn
17202139 H.Shimahara, T.Yoshida, Y.Shibata, M.Shimizu, Y.Kyogoku, F.Sakiyama, T.Nakazawa, S.Tate, S.Y.Ohki, T.Kato, H.Moriyama, K.Kishida, Y.Tano, T.Ohkubo, and Y.Kobayashi (2007).
Tautomerism of histidine 64 associated with proton transfer in catalysis of carbonic anhydrase.
  J Biol Chem, 282, 9646-9656.  
17427958 I.Elder, Z.Fisher, P.J.Laipis, C.Tu, R.McKenna, and D.N.Silverman (2007).
Structural and kinetic analysis of proton shuttle residues in the active site of human carbonic anhydrase III.
  Proteins, 68, 337-343.
PDB codes: 2hfw 2hfx 2hfy 3uyn 3uyq
17165785 D.Riccardi, P.König, X.Prat-Resina, H.Yu, M.Elstner, T.Frauenheim, and Q.Cui (2006).
"Proton holes" in long-range proton transfer reactions in solution and enzymes: A theoretical analysis.
  J Am Chem Soc, 128, 16302-16311.  
  16511248 M.Budayova-Spano, S.Z.Fisher, M.T.Dauvergne, M.Agbandje-McKenna, D.N.Silverman, D.A.Myles, and R.McKenna (2006).
Production and X-ray crystallographic analysis of fully deuterated human carbonic anhydrase II.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 62, 6-9.
PDB code: 2ax2
16405327 P.H.König, N.Ghosh, M.Hoffmann, M.Elstner, E.Tajkhorshid, T.Frauenheim, and Q.Cui (2006).
Toward theoretical analysis of long-range proton transfer kinetics in biomolecular pumps.
  J Phys Chem A, 110, 548-563.  
  16820676 S.Z.Fisher, L.Govindasamy, N.Boyle, M.Agbandje-McKenna, D.N.Silverman, G.M.Blackburn, and R.McKenna (2006).
X-ray crystallographic studies reveal that the incorporation of spacer groups in carbonic anhydrase inhibitors causes alternate binding modes.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 62, 618-622.
PDB codes: 2eu2 2eu3
16106378 D.Bhatt, C.Tu, S.Z.Fisher, J.A.Hernandez Prada, R.McKenna, and D.N.Silverman (2005).
Proton transfer in a Thr200His mutant of human carbonic anhydrase II.
  Proteins, 61, 239-245.
PDB codes: 1yo0 1yo1 1yo2
16261552 J.F.Eichler, J.C.Cramer, K.L.Kirk, and J.G.Bann (2005).
Biosynthetic incorporation of fluorohistidine into proteins in E. coli: a new probe of macromolecular structure.
  Chembiochem, 6, 2170-2173.  
16204892 T.Weaver (2005).
Structure of free fumarase C from Escherichia coli.
  Acta Crystallogr D Biol Crystallogr, 61, 1395-1401.
PDB code: 1yfe
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.