PDBsum entry 1ugc

Lyase

PDB id: 1ugc

Contents

Protein chain

258 a.a. *

Metals

_ZN

_HG

Waters ×110

* Residue conservation analysis

PDB id:

1ugc

Name:

Lyase

Title:

Human carbonic anhydrase ii [hcaii] (E.C.4.2.1.1) mutant with ala 65 replaced by his (a65h)

Structure:

Carbonic anhydrase ii. Chain: a. Engineered: yes. Mutation: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Cell_line: bl21. Gene: caii. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.

Resolution:

2.00Å R-factor: 0.162 R-free: 0.225

Authors:

L.R.Scolnick,D.W.Christianson

Key ref:

L.R.Scolnick and D.W.Christianson (1996). X-ray crystallographic studies of alanine-65 variants of carbonic anhydrase II reveal the structural basis of compromised proton transfer in catalysis. Biochemistry, 35, 16429-16434. PubMed id: 8987974 DOI: 10.1021/bi9617872

Date:

24-Jul-96 Release date: 01-Apr-97

Protein chain

P00918  (CAH2_HUMAN) -  Carbonic anhydrase 2 from Homo sapiens

Seq: 260 a.a.

Struc: 258 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

Enzyme reactions

• Enzyme class 2: E.C.4.2.1.1 - carbonic anhydrase.
• Reaction: hydrogencarbonate + H⁺ = CO2 + H2O
• Cofactor: Zn(2+)
• Enzyme class 3: E.C.4.2.1.69 - cyanamide hydratase.
• Reaction: urea = cyanamide + H2O

Note, where more than one E.C. class is given (as above), each may correspond to a different protein domain or, in the case of polyprotein precursors, to a different mature protein.

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

reference

DOI no: 10.1021/bi9617872

Biochemistry 35:16429-16434 (1996)

PubMed id: 8987974

X-ray crystallographic studies of alanine-65 variants of carbonic anhydrase II reveal the structural basis of compromised proton transfer in catalysis.

L.R.Scolnick, D.W.Christianson.

ABSTRACT

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.