spacer
spacer

PDBsum entry 1dmy

Go to PDB code: 
protein ligands metals Protein-protein interface(s) links
Lyase (oxo-acid) PDB id
1dmy
Jmol
Contents
Protein chains
237 a.a. *
Ligands
AZM ×2
Metals
_ZN ×2
Waters ×100
* Residue conservation analysis
PDB id:
1dmy
Name: Lyase (oxo-acid)
Title: Complex between murine mitochondrial carbonic anyhdrase v and the transition state analogue acetazolamide
Structure: Murine carbonic anhydrase v. Chain: a, b. Synonym: carbonate dehydrogenase, mcavc. Engineered: yes. Mutation: yes
Source: Mus musculus. House mouse. Organism_taxid: 10090. Strain: balb/cj. Cell_line: bl21. Organ: liver. Organelle: mitochondria. Gene: mca5c. Expressed in: escherichia coli.
Resolution:
2.45Å     R-factor:   0.170    
Authors: P.A.Boriack-Sjodin,D.W.Christianson
Key ref: P.A.Boriack-Sjodin et al. (1995). Structure determination of murine mitochondrial carbonic anhydrase V at 2.45-A resolution: implications for catalytic proton transfer and inhibitor design. Proc Natl Acad Sci U S A, 92, 10949-10953. PubMed id: 7479916 DOI: 10.1073/pnas.92.24.10949
Date:
04-Oct-95     Release date:   03-Apr-96    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P23589  (CAH5A_MOUSE) -  Carbonic anhydrase 5A, mitochondrial
Seq:
Struc:
299 a.a.
237 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 2 residue positions (black crosses)

 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!
  Biological process     one-carbon metabolic process   1 term 
  Biochemical function     carbonate dehydratase activity     2 terms  

 

 
    Added reference    
 
 
DOI no: 10.1073/pnas.92.24.10949 Proc Natl Acad Sci U S A 92:10949-10953 (1995)
PubMed id: 7479916  
 
 
Structure determination of murine mitochondrial carbonic anhydrase V at 2.45-A resolution: implications for catalytic proton transfer and inhibitor design.
P.A.Boriack-Sjodin, R.W.Heck, P.J.Laipis, D.N.Silverman, D.W.Christianson.
 
  ABSTRACT  
 
The three-dimensional structure of murine mitochondrial carbonic anhydrase V has been determined and refined at 2.45-A resolution (crystallographic R factor = 0.187). Significant structural differences unique to the active site of carbonic anhydrase V are responsible for differences in the mechanism of catalytic proton transfer as compared with other carbonic anhydrase isozymes. In the prototypical isozyme, carbonic anhydrase II, catalytic proton transfer occurs via the shuttle group His-64; carbonic anhydrase V has Tyr-64, which is not an efficient proton shuttle due in part to the bulky adjacent side chain of Phe-65. Based on analysis of the structure of carbonic anhydrase V, we speculate that Tyr-131 may participate in proton transfer due to its proximity to zinc-bound solvent, its solvent accessibility, and its electrostatic environment in the protein structure. Finally, the design of isozyme-specific inhibitors is discussed in view of the complex between carbonic anhydrase V and acetazolamide, a transition-state analogue. Such inhibitors may be physiologically important in the regulation of blood glucose levels.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
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
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
18931408 J.Jeyakanthan, S.Rangarajan, P.Mridula, S.P.Kanaujia, Y.Shiro, S.Kuramitsu, S.Yokoyama, and K.Sekar (2008).
Observation of a calcium-binding site in the gamma-class carbonic anhydrase from Pyrococcus horikoshii.
  Acta Crystallogr D Biol Crystallogr, 64, 1012-1019.
PDB codes: 1v3w 1v67 2fko
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.  
17407288 D.K.Srivastava, K.M.Jude, A.L.Banerjee, M.Haldar, S.Manokaran, J.Kooren, S.Mallik, and D.W.Christianson (2007).
Structural analysis of charge discrimination in the binding of inhibitors to human carbonic anhydrases I and II.
  J Am Chem Soc, 129, 5528-5537.
PDB codes: 2nmx 2nn1 2nn7 2nng 2nno 2nns 2nnv
15604675 G.Parisi, M.Perales, M.S.Fornasari, A.Colaneri, N.González-Schain, D.Gómez-Casati, S.Zimmermann, A.Brennicke, A.Araya, J.G.Ferry, J.Echave, and E.Zabaleta (2004).
Gamma carbonic anhydrases in plant mitochondria.
  Plant Mol Biol, 55, 193-207.  
12107142 K.S.Smith, C.Ingram-Smith, and J.G.Ferry (2002).
Roles of the conserved aspartate and arginine in the catalytic mechanism of an archaeal beta-class carbonic anhydrase.
  J Bacteriol, 184, 4240-4245.  
12009884 M.Ferraroni, S.Tilli, F.Briganti, W.R.Chegwidden, C.T.Supuran, K.E.Wiebauer, R.E.Tashian, and A.Scozzafava (2002).
Crystal structure of a zinc-activated variant of human carbonic anhydrase I, CA I Michigan 1: evidence for a second zinc binding site involving arginine coordination.
  Biochemistry, 41, 6237-6244.
PDB codes: 1j9w 1jv0
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
10978542 K.S.Smith, and J.G.Ferry (2000).
Prokaryotic carbonic anhydrases.
  FEMS Microbiol Rev, 24, 335-366.  
11073902 K.S.Smith, N.J.Cosper, C.Stalhandske, R.A.Scott, and J.G.Ferry (2000).
Structural and kinetic characterization of an archaeal beta-class carbonic anhydrase.
  J Bacteriol, 182, 6605-6613.  
11032910 M.S.Ghandour, A.K.Parkkila, S.Parkkila, A.Waheed, and W.S.Sly (2000).
Mitochondrial carbonic anhydrase in the nervous system: expression in neuronal and glial cells.
  J Neurochem, 75, 2212-2220.  
10924115 T.M.Iverson, B.E.Alber, C.Kisker, J.G.Ferry, and D.C.Rees (2000).
A closer look at the active site of gamma-class carbonic anhydrases: high-resolution crystallographic studies of the carbonic anhydrase from Methanosarcina thermophila.
  Biochemistry, 39, 9222-9231.
PDB codes: 1qq0 1qre 1qrf 1qrg 1qrl 1qrm
10354450 J.Gao, Q.Wu, J.Carbeck, Q.P.Lei, R.D.Smith, and G.M.Whitesides (1999).
Probing the energetics of dissociation of carbonic anhydrase-ligand complexes in the gas phase.
  Biophys J, 76, 3253-3260.  
10588708 J.Miksovska, M.Schiffer, D.K.Hanson, and P.Sebban (1999).
Proton uptake by bacterial reaction centers: the protein complex responds in a similar manner to the reduction of either quinone acceptor.
  Proc Natl Acad Sci U S A, 96, 14348-14353.  
  10515911 K.S.Smith, and J.G.Ferry (1999).
A plant-type (beta-class) carbonic anhydrase in the thermophilic methanoarchaeon Methanobacterium thermoautotrophicum.
  J Bacteriol, 181, 6247-6253.  
9667939 J.E.Coleman (1998).
Zinc enzymes.
  Curr Opin Chem Biol, 2, 222-234.  
9585580 J.N.Earnhardt, M.Qian, C.Tu, P.J.Laipis, and D.N.Silverman (1998).
Intramolecular proton transfer from multiple sites in catalysis by murine carbonic anhydrase V.
  Biochemistry, 37, 7649-7655.  
  9541386 T.Stams, Y.Chen, P.A.Boriack-Sjodin, J.D.Hurt, J.Liao, J.A.May, T.Dean, P.Laipis, D.N.Silverman, and D.W.Christianson (1998).
Structures of murine carbonic anhydrase IV and human carbonic anhydrase II complexed with brinzolamide: molecular basis of isozyme-drug discrimination.
  Protein Sci, 7, 556-563.
PDB codes: 1a42 2znc 3znc
9265618 F.Briganti, S.Mangani, P.Orioli, A.Scozzafava, G.Vernaglione, and C.T.Supuran (1997).
Carbonic anhydrase activators: X-ray crystallographic and spectroscopic investigations for the interaction of isozymes I and II with histamine.
  Biochemistry, 36, 10384-10392.
PDB code: 1avn
  9371472 S.A.Braus-Stromeyer, G.Schnappauf, G.H.Braus, A.S.Gössner, and H.L.Drake (1997).
Carbonic anhydrase in Acetobacterium woodii and other acetogenic bacteria.
  J Bacteriol, 179, 7197-7200.  
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.  
  8655508 B.E.Alber, and J.G.Ferry (1996).
Characterization of heterologously produced carbonic anhydrase from Methanosarcina thermophila.
  J Bacteriol, 178, 3270-3274.  
8987973 J.E.Jackman, K.M.Merz, and C.A.Fierke (1996).
Disruption of the active site solvent network in carbonic anhydrase II decreases the efficiency of proton transfer.
  Biochemistry, 35, 16421-16428.  
8987974 L.R.Scolnick, and D.W.Christianson (1996).
X-ray crystallographic studies of alanine-65 variants of carbonic anhydrase II reveal the structural basis of compromised proton transfer in catalysis.
  Biochemistry, 35, 16429-16434.
PDB codes: 1uga 1ugb 1ugc 1ugd 1uge 1ugf 1ugg
8794740 R.W.Heck, P.A.Boriack-Sjodin, M.Qian, C.Tu, D.W.Christianson, P.J.Laipis, and D.N.Silverman (1996).
Structure-based design of an intramolecular proton transfer site in murine carbonic anhydrase V.
  Biochemistry, 35, 11605-11611.
PDB code: 1urt
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
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.

 

spacer

spacer