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PDBsum entry 1mua

Go to PDB code: 
protein metals links
Lyase(oxo-acid) PDB id
1mua
Jmol
Contents
Protein chain
256 a.a. *
Metals
_HG
_ZN
Waters ×91
* Residue conservation analysis
PDB id:
1mua
Name: Lyase(oxo-acid)
Title: Structure and energetics of a non-proline cis-peptidyl linkage in an engineered protein
Structure: Carbonic anhydrase ii. Chain: a. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606
Resolution:
1.70Å     R-factor:   0.188    
Authors: S.K.Nair,D.W.Christianson
Key ref:
N.B.Tweedy et al. (1993). Structure and energetics of a non-proline cis-peptidyl linkage in a proline-202-->alanine carbonic anhydrase II variant. Biochemistry, 32, 10944-10949. PubMed id: 8218160 DOI: 10.1021/bi00092a003
Date:
18-Jun-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.
256 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   22 terms 
  Biochemical function     protein binding     5 terms  

 

 
    Added reference    
 
 
DOI no: 10.1021/bi00092a003 Biochemistry 32:10944-10949 (1993)
PubMed id: 8218160  
 
 
Structure and energetics of a non-proline cis-peptidyl linkage in a proline-202-->alanine carbonic anhydrase II variant.
N.B.Tweedy, S.K.Nair, S.A.Paterno, C.A.Fierke, D.W.Christianson.
 
  ABSTRACT  
 
The crystal structure of a human carbonic anhydrase II (CAII) variant, cis-proline-202-->alanine (P202A), has been determined at 1.7-A resolution, indicating that the wild-type geometry, including the cis-peptidyl linkage, is retained upon substitution of proline by alanine. The CO2 hydrase activity and affinity for sulfonamide inhibitors of P202A CAII are virtually identical to those of wild type. However, the substitution of cis-alanine for cis-proline decreases the stability of the folded state by approximately 5 kcal mol-1 relative to both the unfolded state and an equilibrium intermediate in guanidine hydrochloride-induced denaturation. This destabilization can be attributed mainly to the less favorable cis/trans equilibrium of Xaa-alanine bonds compared to Xaa-proline bonds in the denatured state although other factors, including increased conformational entropy of the denatured state and decreased packing interactions in the native state, also contribute to the observed destabilization. The high catalytic activity of P202A CAII illustrates that unfavorable local conformations are nonetheless endured to satisfy the precise structural requirements of catalysis and ligand binding in the CAII active site.
 

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.  
18060825 Y.Jiang, J.T.Su, J.Zhang, X.Wei, Y.B.Yan, and H.M.Zhou (2008).
Reshaping the folding energy landscape of human carbonic anhydrase II by a single point genetic mutation Pro237His.
  Int J Biochem Cell Biol, 40, 776-788.  
16627619 T.U.Schwartz, D.Schmidt, S.G.Brohawn, and G.Blobel (2006).
Homodimerization of the G protein SRbeta in the nucleotide-free state involves proline cis/trans isomerization in the switch II region.
  Proc Natl Acad Sci U S A, 103, 6823-6828.
PDB code: 2ged
16199662 D.A.Schultz, A.M.Friedman, M.A.White, and R.O.Fox (2005).
The crystal structure of the cis-proline to glycine variant (P114G) of ribonuclease A.
  Protein Sci, 14, 2862-2870.
PDB code: 1kh8
15609336 S.Lorenzen, B.Peters, A.Goede, R.Preissner, and C.Frömmel (2005).
Conservation of cis prolyl bonds in proteins during evolution.
  Proteins, 58, 589-595.  
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
  10794421 R.E.Burton, J.A.Hunt, C.A.Fierke, and T.G.Oas (2000).
Novel disulfide engineering in human carbonic anhydrase II using the PAIRWISE side-chain geometry database.
  Protein Sci, 9, 776-785.  
  10739243 W.F.Yu, C.S.Tung, H.Wang, and M.L.Tasayco (2000).
NMR analysis of cleaved Escherichia coli thioredoxin (1-73/74-108) and its P76A variant: cis/trans peptide isomerization.
  Protein Sci, 9, 20-28.  
  10716195 Y.Xiong, D.Juminaga, G.V.Swapna, W.J.Wedemeyer, H.A.Scheraga, and G.T.Montelione (2000).
Solution NMR evidence for a cis Tyr-Ala peptide group in the structure of [Pro93Ala] bovine pancreatic ribonuclease A.
  Protein Sci, 9, 421-426.  
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.  
9893985 L.Birolo, V.N.Malashkevich, G.Capitani, F.De Luca, A.Moretta, J.N.Jansonius, and G.Marino (1999).
Functional and structural analysis of cis-proline mutants of Escherichia coli aspartate aminotransferase.
  Biochemistry, 38, 905-913.
PDB codes: 1bqa 1bqd
  10210189 M.Moutiez, T.V.Burova, T.Haertlé, and E.Quéméneur (1999).
On the non-respect of the thermodynamic cycle by DsbA variants.
  Protein Sci, 8, 106-112.  
10397796 M.Mutter, T.Wöhr, S.Gioria, and M.Keller (1999).
Pseudo-prolines: induction of cis/trans-conformational interconversion by decreased transition state barriers.
  Biopolymers, 51, 121-128.  
  9684895 L.W.Schultz, S.R.Hargraves, T.A.Klink, and R.T.Raines (1998).
Structure and stability of the P93G variant of ribonuclease A.
  Protein Sci, 7, 1620-1625.
PDB code: 3rsp
9063887 K.H.Gardner, M.K.Rosen, and L.E.Kay (1997).
Global folds of highly deuterated, methyl-protonated proteins by multidimensional NMR.
  Biochemistry, 36, 1389-1401.  
9020793 K.Ogasahara, and K.Yutani (1997).
Equilibrium and kinetic analyses of unfolding and refolding for the conserved proline mutants of tryptophan synthase alpha subunit.
  Biochemistry, 36, 932-940.  
9207064 K.P.Pratt, H.C.Côté, D.W.Chung, R.E.Stenkamp, and E.W.Davie (1997).
The primary fibrin polymerization pocket: three-dimensional structure of a 30-kDa C-terminal gamma chain fragment complexed with the peptide Gly-Pro-Arg-Pro.
  Proc Natl Acad Sci U S A, 94, 7176-7181.
PDB codes: 2fib 3fib
9136875 P.Jonasson, G.Aronsson, U.Carlsson, and B.H.Jonsson (1997).
Tertiary structure formation at specific tryptophan side chains in the refolding of human carbonic anhydrase II.
  Biochemistry, 36, 5142-5148.  
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.  
8634286 R.W.Dodge, and H.A.Scheraga (1996).
Folding and unfolding kinetics of the proline-to-alanine mutants of bovine pancreatic ribonuclease A.
  Biochemistry, 35, 1548-1559.  
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
7567959 M.Vanhove, X.Raquet, and J.M.Frère (1995).
Investigation of the folding pathway of the TEM-1 beta-lactamase.
  Proteins, 22, 110-118.  
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.