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PDBsum entry 1heb

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protein metals links
Lyase(oxo-acid) PDB id
1heb
Jmol
Contents
Protein chain
255 a.a. *
Metals
_HG
_ZN
Waters ×107
* Residue conservation analysis
PDB id:
1heb
Name: Lyase(oxo-acid)
Title: Structural consequences of hydrophilic amino-acid substitutions in the hydrophobic pocket of human carbonic anhydrase ii
Structure: Carbonic anhydrase ii. Chain: a. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606
Resolution:
2.00Å     R-factor:   0.180    
Authors: S.K.Nair,D.W.Christianson
Key ref:
S.K.Nair and D.W.Christianson (1993). Structural consequences of hydrophilic amino acid substitutions in the hydrophobic pocket of human carbonic anhydrase II. Biochemistry, 32, 4506-4514. PubMed id: 8485129 DOI: 10.1021/bi00068a005
Date:
16-Jul-92     Release date:   15-Oct-92    
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: 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/bi00068a005 Biochemistry 32:4506-4514 (1993)
PubMed id: 8485129  
 
 
Structural consequences of hydrophilic amino acid substitutions in the hydrophobic pocket of human carbonic anhydrase II.
S.K.Nair, D.W.Christianson.
 
  ABSTRACT  
 
The three-dimensional structures of Leu-198-->Glu, Leu-198-->His, Leu-198-->Arg, and Leu-198-->Ala variants of human carbonic anhydrase II (CAII) have each been determined by X-ray crystallographic methods to a resolution of 2.0 A. The side chain of Leu-198 is located at the mouth of the active site hydrophobic pocket, and this pocket is required for substrate association. Hydrophobic-->hydrophilic amino acid substitutions at the mouth of the pocket decrease kcat/KM for CO2 hydration: the CO2 hydrase activities of Leu-198-->Glu, Leu-198-->His, and Leu-198-->Arg CAIIs are diminished 19-fold, 10-fold, and 17-fold, respectively, relative to the wild-type enzyme; however, the substitution of a compact aliphatic side chain for Leu-198 has a smaller effect on catalysis, in that Leu-198-->Ala CAII exhibits only a 3-fold decrease in CO2 hydrase activity [Krebs, J. F., Rana, F., Dluhy, R. A., & Fierke, C. A. (1993) Biochemistry (preceding paper in this issue)]. It is intriguing that CO2 hydrase activity is not severely diminished in Leu-198-->Arg CAII, even though the side chain of Arg-198 blocks the hydrophobic pocket. Therefore, the bulky side chain of Arg-198 must be reasonably mobile in order to accommodate substrate association. Significantly, a residue larger than the wild-type Leu-198 side chain does not necessarily block the substrate association pocket; e.g., the side chain of Glu-198 packs against a hydrophobic patch, the net result of which is a wider mouth for the pocket.(ABSTRACT TRUNCATED AT 250 WORDS)
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
19520834 B.Sjöblom, M.Polentarutti, and K.Djinovic-Carugo (2009).
Structural study of X-ray induced activation of carbonic anhydrase.
  Proc Natl Acad Sci U S A, 106, 10609-10613.
PDB codes: 2vva 2vvb
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.  
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
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.  
  7757009 T.P.Lo, M.E.Murphy, J.G.Guillemette, M.Smith, and G.D.Brayer (1995).
Replacements in a conserved leucine cluster in the hydrophobic heme pocket of cytochrome c.
  Protein Sci, 4, 198-208.
PDB codes: 1csu 1csv 1csw 1csx
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.