PDBsum entry 1rj5

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protein ligands metals Protein-protein interface(s) links
Lyase PDB id
Protein chains
259 a.a. *
ACY ×2
_ZN ×2
Waters ×90
* Residue conservation analysis
PDB id:
Name: Lyase
Title: Crystal structure of the extracellular domain of murine carb anhydrase xiv
Structure: Carbonic anhydrase xiv. Chain: a, b. Fragment: extracellular domain. Synonym: carbonate dehydratase xiv, ca-xiv. Engineered: yes
Source: Mus musculus. House mouse. Organism_taxid: 10090. Gene: ca14, car14, catm. Expressed in: chlorocebus aethiops. Expression_system_taxid: 9534. Expression_system_cell_line: cos-7.
2.81Å     R-factor:   0.234     R-free:   0.274
Authors: D.A.Whittington,J.H.Grubb,A.Waheed,G.N.Shah,W.S.Sly,D.W.Chri
Key ref:
D.A.Whittington et al. (2004). Expression, assay, and structure of the extracellular domain of murine carbonic anhydrase XIV: implications for selective inhibition of membrane-associated isozymes. J Biol Chem, 279, 7223-7228. PubMed id: 14660577 DOI: 10.1074/jbc.M310809200
18-Nov-03     Release date:   09-Mar-04    
Go to PROCHECK summary

Protein chains
Pfam   ArchSchema ?
Q9WVT6  (CAH14_MOUSE) -  Carbonic anhydrase 14
337 a.a.
259 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.  - Carbonate dehydratase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: H2CO3 = CO2 + H2O
Bound ligand (Het Group name = ACY)
matches with 75.00% similarity
+ H(2)O
      Cofactor: Zn(2+)
Molecule diagrams generated from .mol files obtained from the KEGG ftp site


    Added reference    
DOI no: 10.1074/jbc.M310809200 J Biol Chem 279:7223-7228 (2004)
PubMed id: 14660577  
Expression, assay, and structure of the extracellular domain of murine carbonic anhydrase XIV: implications for selective inhibition of membrane-associated isozymes.
D.A.Whittington, J.H.Grubb, A.Waheed, G.N.Shah, W.S.Sly, D.W.Christianson.
Carbonic anhydrase (CA) XIV is the most recently identified mammalian carbonic anhydrase isozyme, and its presence has been demonstrated in a number of tissues. Full-length CA XIV is a transmembrane protein composed of an extracellular catalytic domain, a single transmembrane helix, and a short intracellular polypeptide segment. The amino acid sequence identity of human CA XIV relative to the other membrane-associated isozymes (CA IV, CA IX, and CA XII) is 34-46%. We report here the expression and purification of both the full-length enzyme and a truncated, secretory form of murine CA XIV. Both forms of this isozyme are highly active, and both show an abrogation of activity in the presence of 0.2% SDS, in contrast to the behavior of murine CA IV. We also report the crystal structure of the extracellular domain of murine CA XIV at 2.8 A resolution and of an enzyme-acetazolamide complex at 2.9 A resolution. The structure shows a monomeric glycoprotein with a topology similar to that of other mammalian CA isozymes. Based on the x-ray crystallographic results, we compare and contrast known structures of membrane-associated CA isozymes to rationalize the structural elements responsible for the SDS resistance of CA IV and to discuss prospects for the design of selective inhibitors of membrane-associated CA isozymes.
  Selected figure(s)  
Figure 2.
FIG. 2. Structure of the murine CA XIV extracellular domain positioned over the cell membrane. The catalytic zinc ion is indicated by an orange sphere. The disulfide bond between Cys-23 and Cys-203 and the N-linked saccharide at Asn-195 are shown in ball-and-stick representation.
Figure 4.
FIG. 4. N-terminal insert of human CA IV relative to human CA XII and murine CA XIV. The CA IV sequence is depicted in red with the side chains labeled, and the CA XII and CA XIV sequences are shown as C traces in blue and green, respectively. The additional intramolecular contacts in CA IV between the N-terminal insert and the 130's loop combined with the additional disulfide bond between Cys-6 and Cys-13 (depicted in gold) stabilize CA IV in the presence of SDS. Inserts in the CA IV sequence are numbered according to the point of insertion with a letter appended (e.g. 11A, 11B, etc.).
  The above figures are reprinted by permission from the ASBMB: J Biol Chem (2004, 279, 7223-7228) copyright 2004.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21515057 F.Carta, V.Garaj, A.Maresca, J.Wagner, B.S.Avvaru, A.H.Robbins, A.Scozzafava, R.McKenna, and C.T.Supuran (2011).
Sulfonamides incorporating 1,3,5-triazine moieties selectively and potently inhibit carbonic anhydrase transmembrane isoforms IX, XII and XIV over cytosolic isoforms I and II: Solution and X-ray crystallographic studies.
  Bioorg Med Chem, 19, 3105-3119.
PDB codes: 3mmf 3mna
20133774 S.Bouyain, and D.J.Watkins (2010).
The protein tyrosine phosphatases PTPRZ and PTPRG bind to distinct members of the contactin family of neural recognition molecules.
  Proc Natl Acad Sci U S A, 107, 2443-2448.
PDB codes: 3jxa 3jxf 3jxg 3jxh 3kld
20939100 S.Kalkhof, S.Haehn, M.Paulsson, N.Smyth, J.Meiler, and A.Sinz (2010).
Computational modeling of laminin N-terminal domains using sparse distance constraints from disulfide bonds and chemical cross-linking.
  Proteins, 78, 3409-3427.  
20505865 V.Alterio, S.M.Monti, E.Truppo, C.Pedone, C.T.Supuran, and G.De Simone (2010).
The first example of a significant active site conformational rearrangement in a carbonic anhydrase-inhibitor adduct: the carbonic anhydrase I-topiramate complex.
  Org Biomol Chem, 8, 3528-3533.
PDB code: 3lxe
19269136 G.Adamus, and L.Karren (2009).
Autoimmunity against carbonic anhydrase II affects retinal cell functions in autoimmune retinopathy.
  J Autoimmun, 32, 133-139.  
19805286 V.Alterio, M.Hilvo, A.Di Fiore, C.T.Supuran, P.Pan, S.Parkkila, A.Scaloni, J.Pastorek, S.Pastorekova, C.Pedone, A.Scozzafava, S.M.Monti, and G.De Simone (2009).
Crystal structure of the catalytic domain of the tumor-associated human carbonic anhydrase IX.
  Proc Natl Acad Sci U S A, 106, 16233-16238.
PDB code: 3iai
18430117 S.Parkkila (2008).
Significance of pH regulation and carbonic anhydrases in tumour progression and implications for diagnostic and therapeutic approaches.
  BJU Int, 101, 16-21.  
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.  
17607683 A.Thiry, B.Masereel, J.M.Dogné, C.T.Supuran, J.Wouters, and C.Michaux (2007).
Exploration of the Binding Mode of Indanesulfonamides as Selective Inhibitors of Human Carbonic Anhydrase Type VII by Targeting Lys 91.
  ChemMedChem, 2, 1273-1280.  
17499996 I.Nishimori, S.Onishi, D.Vullo, A.Innocenti, A.Scozzafava, and C.T.Supuran (2007).
Carbonic anhydrase activators: the first activation study of the human secretory isoform VI with amino acids and amines.
  Bioorg Med Chem, 15, 5351-5357.  
17228367 J.M.Purkerson, A.M.Kittelberger, and G.J.Schwartz (2007).
Basolateral carbonic anhydrase IV in the proximal tubule is a glycosylphosphatidylinositol-anchored protein.
  Kidney Int, 71, 407-416.  
15901897 E.A.Nagelhus, T.M.Mathiisen, A.C.Bateman, F.M.Haug, O.P.Ottersen, J.H.Grubb, A.Waheed, and W.S.Sly (2005).
Carbonic anhydrase XIV is enriched in specific membrane domains of retinal pigment epithelium, Muller cells, and astrocytes.
  Proc Natl Acad Sci U S A, 102, 8030-8035.  
15894606 L.Premkumar, H.M.Greenblatt, U.K.Bageshwar, T.Savchenko, I.Gokhman, J.L.Sussman, and A.Zamir (2005).
Three-dimensional structure of a halotolerant algal carbonic anhydrase predicts halotolerance of a mammalian homolog.
  Proc Natl Acad Sci U S A, 102, 7493-7498.
PDB code: 1y7w
16206834 O.Ozensoy, S.Isik, O.Arslan, M.Arslan, A.Scozzafava, and C.T.Supuran (2005).
Carbonic anhydrase inhibitors. Inhibition of red blood cell ostrich (Struthio camelus) carbonic anhydrase with a series of aromatic and heterocyclic sulfonamides.
  J Enzyme Inhib Med Chem, 20, 383-387.  
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.