PMID- 15049705
OWN - NLM
STAT- MEDLINE
DCOM- 20040729
LR  - 20150604
IS  - 0006-2960 (Print)
IS  - 0006-2960 (Linking)
VI  - 43
IP  - 13
DP  - 2004 Apr 6
TI  - Probing determinants of the metal ion selectivity in carbonic anhydrase using 
      mutagenesis.
PG  - 3979-86
AB  - Few studies measuring thermodynamic metal ion selectivity of metalloproteins have 
      been performed, and the major determinants of metal ion selectivity in proteins 
      are not yet well understood. Several features of metal ion binding sites and 
      metal coordination have been hypothesized to alter the transition metal 
      selectivity of chelators, including (1) the polarizability of the coordinating 
      atom, (2) the relative sizes of the binding site and the metal ion, and (3) the 
      metal ion binding site geometry. To test these hypotheses, we have measured the 
      metal ion affinity and selectivity of a prototypical zinc enzyme, human carbonic 
      anhydrase II (CAII), and a number of active site variants where one of the 
      coordinating ligands is substituted by another side chain capable of coordinating 
      metal. CAII and almost all of the variants follow the inherent metal ion affinity 
      trend suggested by the Irving-Williams series, demonstrating that this trend 
      operates within proteins as well as within small molecule chelators and may be a 
      dominant factor in metal ion selectivity in biology. Neither the polarizability 
      of the liganding side chains nor the size of the metal ion binding site 
      correlates strongly with metal ion specificity; instead, changes in metal ion 
      specificity in the variants correlate with the preferred coordination number and 
      geometry of the metal ion. This correlation suggests that a primary feature 
      driving deviations from the inherent ligand affinity trend is the positioning of 
      active site groups such that a given metal ion can adopt a preferred coordination 
      number/geometry.
FAU - McCall, Keith A
AU  - McCall KA
AD  - Department of Biochemistry, Duke University Medical Center, Box 3711, Durham, 
      North Carolina 27710, USA.
FAU - Fierke, Carol A
AU  - Fierke CA
LA  - eng
GR  - GM 40602/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Biochemistry
JT  - Biochemistry
JID - 0370623
RN  - 0 (Cations, Divalent)
RN  - 0 (Isoenzymes)
RN  - 0 (Ligands)
RN  - 0 (Metalloproteins)
RN  - 0 (Metals, Heavy)
RN  - 00BH33GNGH (Cadmium)
RN  - 3G0H8C9362 (Cobalt)
RN  - 42Z2K6ZL8P (Manganese)
RN  - 4QD397987E (Histidine)
RN  - 789U1901C5 (Copper)
RN  - 7OV03QG267 (Nickel)
RN  - EC 4.2.1.- (Carbonic Anhydrase II)
SB  - IM
MH  - Amino Acid Substitution/genetics
MH  - Binding Sites/genetics
MH  - Cadmium/chemistry
MH  - Carbonic Anhydrase II/*chemistry/*genetics
MH  - Cations, Divalent/chemistry
MH  - Cobalt/chemistry
MH  - Copper/chemistry
MH  - Histidine/genetics
MH  - Humans
MH  - Hydrogen Bonding
MH  - Isoenzymes/chemistry/genetics
MH  - Ligands
MH  - Manganese/chemistry
MH  - Metalloproteins/*chemistry/*genetics
MH  - Metals, Heavy/*chemistry
MH  - *Mutagenesis, Site-Directed
MH  - Nickel/chemistry
MH  - Thermodynamics
EDAT- 2004/03/31 05:00
MHDA- 2004/07/30 05:00
CRDT- 2004/03/31 05:00
PHST- 2004/03/31 05:00 [pubmed]
PHST- 2004/07/30 05:00 [medline]
PHST- 2004/03/31 05:00 [entrez]
AID - 10.1021/bi0498914 [doi]
PST - ppublish
SO  - Biochemistry. 2004 Apr 6;43(13):3979-86. doi: 10.1021/bi0498914.