PMID- 8218160
OWN - NLM
STAT- MEDLINE
DCOM- 19931126
LR  - 20190613
IS  - 0006-2960 (Print)
IS  - 0006-2960 (Linking)
VI  - 32
IP  - 41
DP  - 1993 Oct 19
TI  - Structure and energetics of a non-proline cis-peptidyl linkage in a 
      proline-202-->alanine carbonic anhydrase II variant.
PG  - 10944-9
AB  - The crystal structure of a human carbonic anhydrase II (CAII) variant, 
      cis-proline-202-->alanine (P202A), has been determined at 1.7-A resolution, 
      indicating that the wild-type geometry, including the cis-peptidyl linkage, is 
      retained upon substitution of proline by alanine. The CO2 hydrase activity and 
      affinity for sulfonamide inhibitors of P202A CAII are virtually identical to 
      those of wild type. However, the substitution of cis-alanine for cis-proline 
      decreases the stability of the folded state by approximately 5 kcal mol-1 
      relative to both the unfolded state and an equilibrium intermediate in guanidine 
      hydrochloride-induced denaturation. This destabilization can be attributed mainly 
      to the less favorable cis/trans equilibrium of Xaa-alanine bonds compared to 
      Xaa-proline bonds in the denatured state although other factors, including 
      increased conformational entropy of the denatured state and decreased packing 
      interactions in the native state, also contribute to the observed 
      destabilization. The high catalytic activity of P202A CAII illustrates that 
      unfavorable local conformations are nonetheless endured to satisfy the precise 
      structural requirements of catalysis and ligand binding in the CAII active site.
FAU - Tweedy, N B
AU  - Tweedy NB
AD  - Biochemistry Department, Duke University Medical Center, Durham, North Carolina 
      27710.
FAU - Nair, S K
AU  - Nair SK
FAU - Paterno, S A
AU  - Paterno SA
FAU - Fierke, C A
AU  - Fierke CA
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, P.H.S.
PL  - United States
TA  - Biochemistry
JT  - Biochemistry
JID - 0370623
RN  - 9DLQ4CIU6V (Proline)
RN  - EC 4.2.1.1 (Carbonic Anhydrases)
RN  - OF5P57N2ZX (Alanine)
SB  - IM
MH  - *Alanine
MH  - Binding Sites
MH  - Carbonic Anhydrases/*chemistry/metabolism
MH  - Catalysis
MH  - Crystallography, X-Ray
MH  - Enzyme Stability
MH  - Humans
MH  - Molecular Structure
MH  - *Proline
MH  - Protein Conformation
MH  - Stereoisomerism
MH  - Thermodynamics
EDAT- 1993/10/19 00:00
MHDA- 1993/10/19 00:01
CRDT- 1993/10/19 00:00
PHST- 1993/10/19 00:00 [pubmed]
PHST- 1993/10/19 00:01 [medline]
PHST- 1993/10/19 00:00 [entrez]
AID - 10.1021/bi00092a003 [doi]
PST - ppublish
SO  - Biochemistry. 1993 Oct 19;32(41):10944-9. doi: 10.1021/bi00092a003.