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PDBsum entry 1ydd

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protein ligands metals links
Hydro-lyase PDB id
1ydd
Jmol
Contents
Protein chain
256 a.a. *
Ligands
AZM
Metals
_ZN
_HG
Waters ×101
* Residue conservation analysis
PDB id:
1ydd
Name: Hydro-lyase
Title: Structural basis of inhibitor affinity to variants of human carbonic anhydrase ii
Structure: Carbonic anhydrase ii. Chain: a. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606
Resolution:
2.10Å     R-factor:   0.187    
Authors: S.K.Nair,D.W.Christianson
Key ref:
S.K.Nair et al. (1995). Structural basis of inhibitor affinity to variants of human carbonic anhydrase II. Biochemistry, 34, 3981-3989. PubMed id: 7696263 DOI: 10.1021/bi00012a016
Date:
22-Dec-94     Release date:   14-Feb-95    
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   21 terms 
  Biochemical function     protein binding     5 terms  

 

 
    Added reference    
 
 
DOI no: 10.1021/bi00012a016 Biochemistry 34:3981-3989 (1995)
PubMed id: 7696263  
 
 
Structural basis of inhibitor affinity to variants of human carbonic anhydrase II.
S.K.Nair, J.F.Krebs, D.W.Christianson, C.A.Fierke.
 
  ABSTRACT  
 
The activities and structures of certain L198 variants of human carbonic anhydrase II (CAII) have been reported recently [Krebs, J. F., Rana, F., Dluhy, R. A., & Fierke, C. A. (1993) Biochemistry 32, 4496-4505; Nair, S. K., & Christianson, D. W. (1993) Biochemistry 32, 4506-4514]. In order to understand the structural basis of enzyme-inhibitor affinity, we now report the dissociation rate and equilibrium constants for acetazolamide and dansylamide binding to 13 variants of CAII containing substituted amino acids at position 198. These data indicate that inhibitor affinity is modulated by the hydrophobicity and charge of the 198 side chain. Furthermore, we have determined crystal structures of L198R, L198E, and L198F CAIIs complexed with the transition state analog acetazolamide. The substituted benzyl side chain of L198F CAII does not occlude the substrate association pocket, and it is therefore not surprising that this substitution has minimal effects on catalytic properties and inhibitor binding. Nevertheless, the F198 side chain undergoes a significant conformation change in order to accommodate the binding of acetazolamide; the same behavior is observed for the engineered side chain of L198R CAII. In contrast, the engineered side chain of L198E CAII does not alter its conformation upon inhibitor binding. We conclude that the mobility and hydrophobicity or residue 198 side chains affect enzyme-inhibitor (and enzyme-substrate) affinity, and these structure-function relationships are important for understanding the behavior of carbonic anhydrase isozyme III, which bears a wild-type F198 side chain.(ABSTRACT TRUNCATED AT 250 WORDS)
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
19818877 T.K.Hurst, D.Wang, R.B.Thompson, and C.A.Fierke (2010).
Carbonic anhydrase II-based metal ion sensing: Advances and new perspectives.
  Biochim Biophys Acta, 1804, 393-403.  
  19851004 K.H.Sippel, A.H.Robbins, J.Domsic, C.Genis, M.Agbandje-McKenna, and R.McKenna (2009).
High-resolution structure of human carbonic anhydrase II complexed with acetazolamide reveals insights into inhibitor drug design.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 65, 992-995.
PDB code: 3hs4
19637848 S.E.Hill, J.N.Bandaria, M.Fox, E.Vanderah, A.Kohen, and C.M.Cheatum (2009).
Exploring the molecular origins of protein dynamics in the active site of human carbonic anhydrase II.
  J Phys Chem B, 113, 11505-11510.  
  19956789 S.Manokaran, A.Berg, X.Zhang, W.Chen, and D.K.Srivastava (2008).
Modulation of Ligand Binding Affinity of Tumorigenic Carbonic Anhydrase XII upon Interaction with Cationic CdTe Quantum Dots.
  J Biomed Nanotechnol, 4, 491-498.  
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.  
  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
15772311 M.I.Zavodszky, and L.A.Kuhn (2005).
Side-chain flexibility in protein-ligand binding: the minimal rotation hypothesis.
  Protein Sci, 14, 1104-1114.  
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.  
11330996 C.A.DiTusa, T.Christensen, K.A.McCall, C.A.Fierke, and E.J.Toone (2001).
Thermodynamics of metal ion binding. 1. Metal ion binding by wild-type carbonic anhydrase.
  Biochemistry, 40, 5338-5344.  
11493685 D.A.Whittington, A.Waheed, B.Ulmasov, G.N.Shah, J.H.Grubb, W.S.Sly, and D.W.Christianson (2001).
Crystal structure of the dimeric extracellular domain of human carbonic anhydrase XII, a bitopic membrane protein overexpressed in certain cancer tumor cells.
  Proc Natl Acad Sci U S A, 98, 9545-9550.
PDB codes: 1jcz 1jd0
11180334 S.Grüneberg, B.Wendt, and G.Klebe (2001).
Subnanomolar Inhibitors from Computer Screening: A Model Study Using Human Carbonic Anhydrase II.
  Angew Chem Int Ed Engl, 40, 389-393.  
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.  
9336012 S.Lindskog (1997).
Structure and mechanism of carbonic anhydrase.
  Pharmacol Ther, 74, 1.  
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.