PMID- 1909891
OWN - NLM
STAT- MEDLINE
DCOM- 19911023
LR  - 20190613
IS  - 0006-2960 (Print)
IS  - 0006-2960 (Linking)
VI  - 30
IP  - 38
DP  - 1991 Sep 24
TI  - Conformational mobility of His-64 in the Thr-200----Ser mutant of human carbonic 
      anhydrase II.
PG  - 9153-60
AB  - The three-dimensional structure of the Thr-200----Ser (T200S) mutant of human 
      carbonic anhydrase II (CAII) has been determined by X-ray crystallographic 
      methods at 2.1-A resolution. This particular mutant of CAII exhibits CO2 hydrase 
      activity that is comparable to that of the wild-type enzyme with a 2-fold 
      stabilization of the E.HCO3- complex and esterase activity that is 4-fold greater 
      than that of the wild-type enzyme. The structure of the mutant enzyme reveals no 
      significant local changes accompanying the conservative T200S substitution, but 
      an important nonlocal structural change is evident: the side chain of catalytic 
      residue His-64 rotates away from the active site by 105 degrees about chi 1 and 
      apparently displaces a water molecule. The displaced water molecule is present in 
      the wild-type enzyme; however, the electron density into which this water is 
      built is interpretable as an alternate conformation of His-64 with 10-20% 
      occupancy. The rate constants for proton transfer from the zinc-water ligand to 
      His-64 and from His-64 to bulk solvent are maintained in the T200S variant; 
      therefore, if His-64 is conformationally mobile about chi 1 and/or chi 2 during 
      catalysis, compensatory changes in solvent configuration must sustain efficient 
      proton transfer.
FAU - Krebs, J F
AU  - Krebs JF
AD  - Department of Biochemistry, Duke University Medical Center, Durham, North 
      Carolina 27710.
FAU - Fierke, C A
AU  - Fierke CA
FAU - Alexander, R S
AU  - Alexander RS
FAU - Christianson, D W
AU  - Christianson DW
LA  - eng
GR  - GM40602/GM/NIGMS NIH HHS/United States
GR  - GM45614/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
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 (Ligands)
RN  - 2ZD004190S (Threonine)
RN  - 452VLY9402 (Serine)
RN  - 4QD397987E (Histidine)
RN  - EC 3.1.- (Esterases)
RN  - EC 4.2.1.1 (Carbonic Anhydrases)
RN  - J41CSQ7QDS (Zinc)
SB  - IM
MH  - Carbonic Anhydrases/*chemistry
MH  - Computer Graphics
MH  - DNA Mutational Analysis
MH  - Esterases/chemistry
MH  - Fourier Analysis
MH  - Histidine/chemistry
MH  - Humans
MH  - Hydrogen-Ion Concentration
MH  - Kinetics
MH  - Ligands
MH  - Motion
MH  - Protein Conformation
MH  - Serine/chemistry
MH  - Structure-Activity Relationship
MH  - Threonine/chemistry
MH  - Zinc/chemistry
EDAT- 1991/09/24 00:00
MHDA- 1991/09/24 00:01
CRDT- 1991/09/24 00:00
PHST- 1991/09/24 00:00 [pubmed]
PHST- 1991/09/24 00:01 [medline]
PHST- 1991/09/24 00:00 [entrez]
AID - 10.1021/bi00102a005 [doi]
PST - ppublish
SO  - Biochemistry. 1991 Sep 24;30(38):9153-60. doi: 10.1021/bi00102a005.