PDBsum entry 1bnt

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Lyase PDB id
Protein chain
256 a.a. *
Waters ×61
* Residue conservation analysis
PDB id:
Name: Lyase
Title: Carbonic anhydrase ii inhibitor
Structure: Carbonic anhydrase. Chain: a. Ec:
Source: Homo sapiens. Human. Organism_taxid: 9606. Cell: erythrocytes. Cellular_location: cytoplasm
2.15Å     R-factor:   0.165    
Authors: P.A.Boriack-Sjodin,S.Zeitlin,D.W.Christianson
Key ref:
P.A.Boriack-Sjodin et al. (1998). Structural analysis of inhibitor binding to human carbonic anhydrase II. Protein Sci, 7, 2483-2489. PubMed id: 9865942 DOI: 10.1002/pro.5560071201
30-Jul-98     Release date:   15-Jun-99    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
P00918  (CAH2_HUMAN) -  Carbonic anhydrase 2
260 a.a.
256 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.  - Carbonate dehydratase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: H2CO3 = CO2 + H2O
= 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: 10.1002/pro.5560071201 Protein Sci 7:2483-2489 (1998)
PubMed id: 9865942  
Structural analysis of inhibitor binding to human carbonic anhydrase II.
P.A.Boriack-Sjodin, S.Zeitlin, H.H.Chen, L.Crenshaw, S.Gross, A.Dantanarayana, P.Delgado, J.A.May, T.Dean, D.W.Christianson.
X-ray crystal structures of carbonic anhydrase II (CAII) complexed with sulfonamide inhibitors illuminate the structural determinants of high affinity binding in the nanomolar regime. The primary binding interaction is the coordination of a primary sulfonamide group to the active site zinc ion. Secondary interactions fine-tune tight binding in regions of the active site cavity >5 A away from zinc, and this work highlights three such features: (1) advantageous conformational restraints of a bicyclic thienothiazene-6-sulfonamide-1,1-dioxide inhibitor skeleton in comparison with a monocyclic 2,5-thiophenedisulfonamide skeleton; (2) optimal substituents attached to a secondary sulfonamide group targeted to interact with hydrophobic patches defined by Phe131, Leu198, and Pro202; and (3) optimal stereochemistry and configuration at the C-4 position of bicyclic thienothiazene-6-sulfonamides; the C-4 substituent can interact with His64, the catalytic proton shuttle. Structure-activity relationships rationalize affinity trends observed during the development of brinzolamide (Azopt), the newest carbonic anhydrase inhibitor approved for the treatment of glaucoma.
  Selected figure(s)  
Figure 3.
Fig. 3. Superposition of theatomiccoordinates of AL5300 (gree)and AL5415 (red).Forclarity, only theproteinatoms of CAII inthe CAII- AL5415complexareshown Primarysulfonamide-zinccoordi- nationgeometry,andedge-to-faceinteractionsbetweenthethophene ``tail'' of theinhibitorand Phel31, areidenticalinthetwo complees. Binding differenceare localized totheConformationofthesecondarysulfonamide group.
Figure 6.
Fig. 6. Superpositionoftheatomiccoordinatesofbrinzolamide(Azoptm; AL4862, Kd = 0.13 nM) anddorzolamide(Trusoptm, Ki 0.37 nM, Greer et l., 994; Smithet al., 1994). thetwonewest CAII inhibitorsappoved for the treatmentofglaucoma.Brinzolamideisred;dorzolaide is green. Forclarity,onlytheproteinatomsoCAII in the CAII-L4862 (brizola- mide)complex are shown(yellow).Notethatthesix-memberedthiazene ring of rizolamideadopts a half-chair,conformation,whereasthesix- membeedthienoringofdorzolamideadopts a half-chair2conformation.
  The above figures are reprinted from an Open Access publication published by the Protein Society: Protein Sci (1998, 7, 2483-2489) copyright 1998.  
  Figures were selected by an automated process.  

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.  
17910057 A.Amini, P.J.Shrimpton, S.H.Muggleton, and M.J.Sternberg (2007).
A general approach for developing system-specific functions to score protein-ligand docked complexes using support vector inductive logic programming.
  Proteins, 69, 823-831.  
16506782 K.M.Jude, A.L.Banerjee, M.K.Haldar, S.Manokaran, B.Roy, S.Mallik, D.K.Srivastava, and D.W.Christianson (2006).
Ultrahigh resolution crystal structures of human carbonic anhydrases I and II complexed with "two-prong" inhibitors reveal the molecular basis of high affinity.
  J Am Chem Soc, 128, 3011-3018.
PDB codes: 2foq 2fos 2fou 2fov 2foy
15526325 M.Kontoyianni, G.S.Sokol, and L.M.McClellan (2005).
Evaluation of library ranking efficacy in virtual screening.
  J Comput Chem, 26, 11-22.  
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.  
  10794420 J.Shimada, A.V.Ishchenko, and E.I.Shakhnovich (2000).
Analysis of knowledge-based protein-ligand potentials using a self-consistent method.
  Protein Sci, 9, 765-775.  
10614682 M.F.Sugrue (2000).
Pharmacological and ocular hypotensive properties of topical carbonic anhydrase inhibitors.
  Prog Retin Eye Res, 19, 87.  
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.