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PDBsum entry 1uga

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protein metals links
Lyase (oxo-acid) PDB id
1uga
Jmol
Contents
Protein chain
258 a.a. *
Metals
_ZN
Waters ×121
* Residue conservation analysis
PDB id:
1uga
Name: Lyase (oxo-acid)
Title: Human carbonic anhydrase ii[hcaii] (E.C.4.2.1.1) mutant with ala 65 replaced by phe (a65f)
Structure: Carbonic anhydrase ii. Chain: a. Engineered: yes. Mutation: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: caii. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.
Resolution:
2.00Å     R-factor:   0.154     R-free:   0.246
Authors: L.R.Scolnick,D.W.Christianson
Key ref:
L.R.Scolnick and D.W.Christianson (1996). X-ray crystallographic studies of alanine-65 variants of carbonic anhydrase II reveal the structural basis of compromised proton transfer in catalysis. Biochemistry, 35, 16429-16434. PubMed id: 8987974 DOI: 10.1021/bi9617872
Date:
24-Jul-96     Release date:   27-Jan-97    
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
* 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: 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/bi9617872 Biochemistry 35:16429-16434 (1996)
PubMed id: 8987974  
 
 
X-ray crystallographic studies of alanine-65 variants of carbonic anhydrase II reveal the structural basis of compromised proton transfer in catalysis.
L.R.Scolnick, D.W.Christianson.
 
  ABSTRACT  
 
The three-dimensional structures of A65F, A65L, A65H, A65T, A65S, and A65G human carbonic anhydrase II (CAII) variants have been solved by X-ray crystallographic methods to probe the importance of residue 65 and the structural implications of its evolutionary drift in the greater family of carbonic anhydrase isozymes. Structure-activity relationships in this series of CAII variants are correlated with those established for other carbonic anhydrase isozymes. We conclude that a bulky side chain at position 65 hinders the formation of an effective solvent bridge between zinc-bound water and H64 and thereby hinders solvent-mediated proton transfer between these two groups [Jackman, J. E., Merz, K. M., Jr., & Fierke, C. A. (1996) Biochemistry 35, 16421-16428]. Despite the introduction of a polar hydroxyl group at this position, smaller side chains such as serine or threonine substituted for A65 do not perturb the formation of a solvent bridge between H64 and zinc-bound solvent. Thus, the evolution of residue 65 size is one factor affecting the trajectory of catalytic proton transfer.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
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.  
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.  
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.  
17387667 S.Yan, L.Zhang, R.I.Cukier, and Y.Bu (2007).
Exploration on regulating factors for proton transfer along hydrogen-bonded water chains.
  Chemphyschem, 8, 944-954.  
16416502 K.Okrasa, and R.J.Kazlauskas (2006).
Manganese-substituted carbonic anhydrase as a new peroxidase.
  Chemistry, 12, 1587-1596.  
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
  11680850 S.P.Ryder, A.K.Oyelere, J.L.Padilla, D.Klostermeier, D.P.Millar, and S.A.Strobel (2001).
Investigation of adenosine base ionization in the hairpin ribozyme by nucleotide analog interference mapping.
  RNA, 7, 1454-1463.  
10336637 B.Elleby, B.Sjöblom, and S.Lindskog (1999).
Changing the efficiency and specificity of the esterase activity of human carbonic anhydrase II by site-specific mutagenesis.
  Eur J Biochem, 262, 516-521.  
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.  
9635771 C.Tu, M.Qian, J.N.Earnhardt, P.J.Laipis, and D.N.Silverman (1998).
Properties of intramolecular proton transfer in carbonic anhydrase III.
  Biophys J, 74, 3182-3189.  
9585580 J.N.Earnhardt, M.Qian, C.Tu, P.J.Laipis, and D.N.Silverman (1998).
Intramolecular proton transfer from multiple sites in catalysis by murine carbonic anhydrase V.
  Biochemistry, 37, 7649-7655.  
8987973 J.E.Jackman, K.M.Merz, and C.A.Fierke (1996).
Disruption of the active site solvent network in carbonic anhydrase II decreases the efficiency of proton transfer.
  Biochemistry, 35, 16421-16428.  
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.