PMID- 8987974
OWN - NLM
STAT- MEDLINE
DCOM- 19970130
LR  - 20141120
IS  - 0006-2960 (Print)
IS  - 0006-2960 (Linking)
VI  - 35
IP  - 51
DP  - 1996 Dec 24
TI  - X-ray crystallographic studies of alanine-65 variants of carbonic anhydrase II 
      reveal the structural basis of compromised proton transfer in catalysis.
PG  - 16429-34
AB  - The three-dimensional structures of A65F, A65L, A65H, A65T, A65S, and A65G human 
      carbonic anhydrase II (CAII) variants have been solved by X-ray crystallographic 
      methods to probe the importance of residue 65 and the structural implications of 
      its evolutionary drift in the greater family of carbonic anhydrase isozymes. 
      Structure-activity relationships in this series of CAII variants are correlated 
      with those established for other carbonic anhydrase isozymes. We conclude that a 
      bulky side chain at position 65 hinders the formation of an effective solvent 
      bridge between zinc-bound water and H64 and thereby hinders solvent-mediated 
      proton transfer between these two groups [Jackman, J. E., Merz, K. M., Jr., & 
      Fierke, C. A. (1996) Biochemistry 35, 16421-16428]. Despite the introduction of a 
      polar hydroxyl group at this position, smaller side chains such as serine or 
      threonine substituted for A65 do not perturb the formation of a solvent bridge 
      between H64 and zinc-bound solvent. Thus, the evolution of residue 65 size is one 
      factor affecting the trajectory of catalytic proton transfer.
FAU - Scolnick, L R
AU  - Scolnick LR
AD  - Department of Chemistry, University of Pennsylvania, Philadelphia 19104-6323, 
      USA.
FAU - Christianson, D W
AU  - Christianson DW
LA  - eng
GR  - GM07229/GM/NIGMS NIH HHS/United States
GR  - GM45614/GM/NIGMS NIH HHS/United States
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Biochemistry
JT  - Biochemistry
JID - 0370623
RN  - 0 (Protons)
RN  - 0 (Recombinant Proteins)
RN  - EC 4.2.1.1 (Carbonic Anhydrases)
RN  - OF5P57N2ZX (Alanine)
SB  - IM
MH  - Alanine/chemistry/genetics
MH  - Animals
MH  - Binding Sites
MH  - Carbonic Anhydrases/*chemistry/genetics/metabolism
MH  - Crystallography, X-Ray
MH  - Evolution, Molecular
MH  - Genetic Variation
MH  - Humans
MH  - In Vitro Techniques
MH  - Models, Molecular
MH  - Molecular Structure
MH  - Protein Conformation
MH  - Protons
MH  - Recombinant Proteins/chemistry/genetics/metabolism
EDAT- 1996/12/24 00:00
MHDA- 1996/12/24 00:01
CRDT- 1996/12/24 00:00
PHST- 1996/12/24 00:00 [pubmed]
PHST- 1996/12/24 00:01 [medline]
PHST- 1996/12/24 00:00 [entrez]
AID - bi9617872 [pii]
AID - 10.1021/bi9617872 [doi]
PST - ppublish
SO  - Biochemistry. 1996 Dec 24;35(51):16429-34. doi: 10.1021/bi9617872.