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PDBsum entry 1cva

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protein ligands metals links
Lyase(oxo-acid) PDB id
1cva
Jmol
Contents
Protein chain
255 a.a. *
Ligands
AZI
Metals
_ZN
Waters ×94
* Residue conservation analysis
PDB id:
1cva
Name: Lyase(oxo-acid)
Title: Structural and functional importance of a conserved hydrogen bond network in human carbonic anhydrase ii
Structure: Carbonic anhydrase ii. Chain: a. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606
Resolution:
2.25Å     R-factor:   0.173    
Authors: J.A.Ippolito,D.W.Christianson
Key ref: J.F.Krebs et al. (1993). Structural and functional importance of a conserved hydrogen bond network in human carbonic anhydrase II. J Biol Chem, 268, 27458-27466. PubMed id: 8262987
Date:
04-Feb-93     Release date:   31-Oct-93    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P00918  (CAH2_HUMAN) -  Carbonic anhydrase 2
Seq:
Struc:
260 a.a.
255 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 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: Zinc
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     extracellular space   10 terms 
  Biological process     angiotensin-mediated signaling pathway   20 terms 
  Biochemical function     protein binding     5 terms  

 

 
    Added reference    
 
 
J Biol Chem 268:27458-27466 (1993)
PubMed id: 8262987  
 
 
Structural and functional importance of a conserved hydrogen bond network in human carbonic anhydrase II.
J.F.Krebs, J.A.Ippolito, D.W.Christianson, C.A.Fierke.
 
  ABSTRACT  
 
Amino acid substitutions at Thr199 of human carbonic anhydrase II (CAII) (Thr199-->Ser, Ala, Val, and Pro) were characterized to investigate the importance of a conserved hydrogen bonding network. The three-dimensional structures of azide-bound and sulfate-bound T199V CAIIs were determined by x-ray crystallographic methods at 2.25 and 2.4 A, respectively (final crystallographic R factors are 0.173 and 0.174, respectively). The CO2 hydrase activities of T199S and T199P variants suggest that the side chain methyl and backbone amino functionalities stabilize the transition state by approximately 0.4 and 0.8 kcal/mol, respectively. The side chain hydroxyl group causes: stabilization of zinc-hydroxide relative to zinc-water (pKa increases approximately 2 units); stabilization of the transition state for bicarbonate dehydration relative to the CAII.HCO3- complex (approximately 5 kcal/mol); and destabilization of the CAII.HCO3- complex (approximately 0.8 kcal/mol). An inverse correlation between log(kcatCO2/KM) and the pKa of zinc-water (r = 0.95, slope = -1) indicates that the hydrogen bonding network stabilizes the chemical transition state and zinc-hydroxide similarly. These data are consistent with the hydroxyl group of Thr199 forming a hydrogen bond with the transition state and a non-hydrogen-bonded van der Waals contact with CAII.HCO3-.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
21053939 E.M.Stone, L.Chantranupong, and G.Georgiou (2010).
The second-shell metal ligands of human arginase affect coordination of the nucleophile and substrate.
  Biochemistry, 49, 10582-10588.  
19747990 J.G.Ferry (2010).
The gamma class of carbonic anhydrases.
  Biochim Biophys Acta, 1804, 374-381.  
19706507 C.L.Berthold, H.Wang, S.Nordlund, and M.Högbom (2009).
Mechanism of ADP-ribosylation removal revealed by the structure and ligand complexes of the dimanganese mono-ADP-ribosylhydrolase DraG.
  Proc Natl Acad Sci U S A, 106, 14247-14252.
PDB codes: 2woc 2wod 2woe
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.  
17573429 S.Marino, K.Hayakawa, K.Hatada, M.Benfatto, A.Rizzello, M.Maffia, and L.Bubacco (2007).
Structural features that govern enzymatic activity in carbonic anhydrase from a low-temperature adapted fish, Chionodraco hamatus.
  Biophys J, 93, 2781-2790.  
17441142 V.M.Krishnamurthy, B.R.Bohall, C.Y.Kim, D.T.Moustakas, D.W.Christianson, and G.M.Whitesides (2007).
Thermodynamic parameters for the association of fluorinated benzenesulfonamides with bovine carbonic anhydrase II.
  Chem Asian J, 2, 94.  
16688707 A.Fernández-Gacio, A.Codina, J.Fastrez, O.Riant, and P.Soumillion (2006).
Transforming carbonic anhydrase into epoxide synthase by metal exchange.
  Chembiochem, 7, 1013-1016.  
15568024 A.Aharoni, L.Gaidukov, O.Khersonsky, S.McQ Gould, C.Roodveldt, and D.S.Tawfik (2005).
The 'evolvability' of promiscuous protein functions.
  Nat Genet, 37, 73-76.  
12056894 S.Huang, B.Sjöblom, A.E.Sauer-Eriksson, and B.H.Jonsson (2002).
Organization of an efficient carbonic anhydrase: implications for the mechanism based on structure-function studies of a T199P/C206S mutant.
  Biochemistry, 41, 7628-7635.
PDB codes: 1lg5 1lg6 1lgd
11330997 C.A.DiTusa, K.A.McCall, T.Christensen, M.Mahapatro, C.A.Fierke, and E.J.Toone (2001).
Thermodynamics of metal ion binding. 2. Metal ion binding by carbonic anhydrase variants.
  Biochemistry, 40, 5345-5351.  
10872443 D.W.Christianson, and J.D.Cox (1999).
Catalysis by metal-activated hydroxide in zinc and manganese metalloenzymes.
  Annu Rev Biochem, 68, 33-57.  
10413479 J.A.Hunt, M.Ahmed, and C.A.Fierke (1999).
Metal binding specificity in carbonic anhydrase is influenced by conserved hydrophobic core residues.
  Biochemistry, 38, 9054-9062.  
9778351 A.Peracchi, A.Karpeisky, L.Maloney, L.Beigelman, and D.Herschlag (1998).
A core folding model for catalysis by the hammerhead ribozyme accounts for its extraordinary sensitivity to abasic mutations.
  Biochemistry, 37, 14765-14775.  
9601024 L.A.Klumb, V.Chu, and P.S.Stayton (1998).
Energetic roles of hydrogen bonds at the ureido oxygen binding pocket in the streptavidin-biotin complex.
  Biochemistry, 37, 7657-7663.  
9336012 S.Lindskog (1997).
Structure and mechanism of carbonic anhydrase.
  Pharmacol Ther, 74, 1.  
9054574 T.T.Baird, A.Waheed, T.Okuyama, W.S.Sly, and C.A.Fierke (1997).
Catalysis and inhibition of human carbonic anhydrase IV.
  Biochemistry, 36, 2669-2678.  
8639494 C.C.Huang,, C.A.Lesburg, L.L.Kiefer, C.A.Fierke, and D.W.Christianson (1996).
Reversal of the hydrogen bond to zinc ligand histidine-119 dramatically diminishes catalysis and enhances metal equilibration kinetics in carbonic anhydrase II.
  Biochemistry, 35, 3439-3446.
PDB codes: 1zsa 1zsb 1zsc
8942988 S.Tamai, A.Waheed, L.B.Cody, and W.S.Sly (1996).
Gly-63-->Gln substitution adjacent to His-64 in rodent carbonic anhydrase IVs largely explains their reduced activity.
  Proc Natl Acad Sci U S A, 93, 13647-13652.  
8942978 T.Stams, S.K.Nair, T.Okuyama, A.Waheed, W.S.Sly, and D.W.Christianson (1996).
Crystal structure of the secretory form of membrane-associated human carbonic anhydrase IV at 2.8-A resolution.
  Proc Natl Acad Sci U S A, 93, 13589-13594.
PDB code: 1znc
7878054 A.Chilkoti, P.H.Tan, and P.S.Stayton (1995).
Site-directed mutagenesis studies of the high-affinity streptavidin-biotin complex: contributions of tryptophan residues 79, 108, and 120.
  Proc Natl Acad Sci U S A, 92, 1754-1758.  
7761440 J.A.Ippolito, T.T.Baird, S.A.McGee, D.W.Christianson, and C.A.Fierke (1995).
Structure-assisted redesign of a protein-zinc-binding site with femtomolar affinity.
  Proc Natl Acad Sci U S A, 92, 5017-5021.
PDB codes: 1ccs 1cct 1ccu
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.