1ZNC

HUMAN CARBONIC ANHYDRASE IV


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.80 Å
  • R-Value Free: 0.252 
  • R-Value Work: 0.197 
  • R-Value Observed: 0.197 

wwPDB Validation   3D Report Full Report


This is version 1.2 of the entry. See complete history


Literature

Crystal structure of the secretory form of membrane-associated human carbonic anhydrase IV at 2.8-A resolution.

Stams, T.Nair, S.K.Okuyama, T.Waheed, A.Sly, W.S.Christianson, D.W.

(1996) Proc Natl Acad Sci U S A 93: 13589-13594

  • DOI: https://doi.org/10.1073/pnas.93.24.13589
  • Primary Citation of Related Structures:  
    1ZNC

  • PubMed Abstract: 

    It has recently been demonstrated that the C-terminal deletion mutant of recombinant human carbonic anhydrase IV (G267X CA IV) converts the normally glycosylphosphatidylinositol-anchored enzyme into a soluble secretory form which has the same catalytic properties as the membrane-associated enzyme purified from human tissues. We have determined the three-dimensional structure of the secretory form of human CA IV by x-ray crystallographic methods to a resolution of 2.8 A. Although the zinc binding site and the hydrophobic substrate binding pocket of CA IV are generally similar to those of other mammalian isozymes, unique structural differences are found elsewhere in the active site. Two disufide linkages, Cys-6-Cys-11G and Cys-23-Cys-203, stabilize the conformation of the N-terminal domain. The latter disulfide additionally stabilizes an active site loop containing a cis-peptide linkage between Pro-201 and Thr-202 (this loop contains catalytic residue Thr-199). On the opposite side of the active site, the Val-131-Asp-136 segment adopts an extended loop conformation instead of an alpha-helix conformation as found in other isozymes. Finally, the C terminus is surrounded by a substantial electropositive surface potential, which is likely to stabilize the interaction of CA IV with the negatively charged phospholipid headgroups of the membrane. These structural features are unique to CA IV and provide a framework for the design of sulfonamide inhibitors selective for this particular isozyme.


  • Organizational Affiliation

    Department of Chemistry, University of Pennsylvania, Philadelphia 19104-6323, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
CARBONIC ANHYDRASE IV
A, B
266Homo sapiensMutation(s): 0 
Gene Names: HUMAN CAIV
EC: 4.2.1.1
UniProt & NIH Common Fund Data Resources
Find proteins for P22748 (Homo sapiens)
Explore P22748 
Go to UniProtKB:  P22748
PHAROS:  P22748
GTEx:  ENSG00000167434 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP22748
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Binding Affinity Annotations 
IDSourceBinding Affinity
SO4 BindingDB:  1ZNC Ki: min: 9.00e+6, max: 4.40e+7 (nM) from 2 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.80 Å
  • R-Value Free: 0.252 
  • R-Value Work: 0.197 
  • R-Value Observed: 0.197 
  • Space Group: C 1 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 89.5α = 90
b = 47.7β = 106.3
c = 141γ = 90
Software Package:
Software NamePurpose
MOSFLMdata reduction
ROTAVATA/AGROVATAdata reduction
X-PLORmodel building
X-PLORrefinement
CCP4data scaling
ROTAVATA)data scaling
X-PLORphasing

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 1997-09-17
    Type: Initial release
  • Version 1.1: 2008-03-24
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance