PDBsum entry 2fr5

Hydrolase

PDB id: 2fr5

Contents

Protein chains

136 a.a. *

Ligands

SO4

TYU ×4

Metals

_ZN ×4

Waters ×500

* Residue conservation analysis

PDB id:

2fr5

Name:

Hydrolase

Title:

Crystal structure of mouse cytidine deaminase complexed with tetrahydrouridine

Structure:

Cytidine deaminase. Chain: a, b, c, d. Synonym: cytidine aminohydrolase. Engineered: yes

Source:

Mus musculus. House mouse. Organism_taxid: 10090. Expressed in: escherichia coli bl21. Expression_system_taxid: 511693.

Biol. unit:

Tetramer (from PQS)

Resolution:

1.48Å R-factor: 0.169 R-free: 0.190

Authors:

A.H.Teh

Key ref:

A.H.Teh et al. (2006). The 1.48 A resolution crystal structure of the homotetrameric cytidine deaminase from mouse. Biochemistry, 45, 7825-7833. PubMed id: 16784234 DOI: 10.1021/bi060345f

Date:

19-Jan-06 Release date: 11-Jul-06

Protein chains

P56389  (CDD_MOUSE) -  Cytidine deaminase from Mus musculus

Seq: 146 a.a.

Struc: 136 a.a.

Enzyme reactions

• Enzyme class: E.C.3.5.4.5 - cytidine deaminase.
• Reaction:
  1. cytidine + H2O + H⁺ = uridine + NH4⁺
  2. 2'-deoxycytidine + H2O + H⁺ = 2'-deoxyuridine + NH4⁺

cytidine + H2O + H(+) = uridine + NH4(+) (Bound ligand (Het Group name = TYU) corresponds exactly)

2'-deoxycytidine + H2O + H(+) = 2'-deoxyuridine (Bound ligand (Het Group name = TYU) matches with 94.12% similarity) + NH4(+)

• Cofactor: Zn(2+)

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

reference

DOI no: 10.1021/bi060345f

Biochemistry 45:7825-7833 (2006)

PubMed id: 16784234

The 1.48 A resolution crystal structure of the homotetrameric cytidine deaminase from mouse.

A.H.Teh, M.Kimura, M.Yamamoto, N.Tanaka, I.Yamaguchi, T.Kumasaka.

ABSTRACT

Cytidine deaminase (CDA) is a zinc-dependent enzyme that catalyzes the deamination of cytidine or deoxycytidine to form uridine or deoxyuridine. Here we present the crystal structure of mouse CDA (MmCDA), complexed with either tetrahydrouridine (THU), 3-deazauridine (DAU), or cytidine. In the MmCDA-DAU complex, it clearly demonstrates that cytidine is distinguished from uridine by its 4-NH(2) group that acts as a hydrogen bond donor. In the MmCDA-cytidine complex, cytidine, unexpectedly, binds as the substrate instead of the deaminated product in three of the four subunits, and in the remaining subunit it binds as the product uridine. Furthermore, the charge-neutralizing Arg68 of MmCDA has also exhibited two alternate conformations, I and II. In conformation I, the only conformation observed in the other structurally known homotetrameric CDAs, Arg68 hydrogen bonds Cys65 and Cys102 to modulate part of their negative charges. However, in conformation II the side chain of Arg68 rotates about 130 degrees around the Cgamma-Cdelta bond and abolishes these hydrogen bonds. The lack of hydrogen bonding may indirectly weaken the zinc-product interaction by increased electron donation from cysteine to the zinc ion, suggesting a novel product-expelling mechanism. On the basis of known structures, structural analysis further reveals two subclasses of homotetrameric CDAs that can be identified according to the position of the charge-neutralizing arginine residue. Implications for CDA-RNA interaction have also been considered.