PDBsum entry 5w10

Hydrolase

PDB id: 5w10

Contents

Protein chains

173 a.a.

Ligands

CMP ×4

Waters ×346

PDB id:

5w10

Name:

Hydrolase

Title:

Lcd1 gaf domain in complex with camp ligand

Structure:

Cgmp-specific phosphodiesterase. Chain: a, b, c, d. Engineered: yes

Source:

Leptospira interrogans serogroup icterohaemorrhagiae serovar copenhageni (strain fiocruz l1-130). Organism_taxid: 267671. Strain: fiocruz l1-130. Gene: lic_13137. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

2.15Å R-factor: 0.196 R-free: 0.225

Authors:

C.R.Guzzo,N.K.Maciel,A.S.Barbosa,C.S.Farah

Key ref:

F.N.da Costa Vasconcelos et al. (2017). Structural and Enzymatic Characterization of a cAMP-Dependent Diguanylate Cyclase from Pathogenic Leptospira Species. J Mol Biol, 429, 2337-2352. PubMed id: 28601495 DOI: 10.1016/j.jmb.2017.06.002

Date:

01-Jun-17 Release date: 28-Jun-17

Protein chains

Q72MQ6  (Q72MQ6_LEPIC) -  cGMP-specific phosphodiesterase from Leptospira interrogans serogroup Icterohaemorrhagiae serovar copenhageni (strain Fiocruz L1-130)

Seq: 327 a.a.

Struc: 173 a.a.

DOI no: 10.1016/j.jmb.2017.06.002

J Mol Biol 429:2337-2352 (2017)

PubMed id: 28601495

Structural and Enzymatic Characterization of a cAMP-Dependent Diguanylate Cyclase from Pathogenic Leptospira Species.

F.N.da Costa Vasconcelos, N.K.Maciel, D.C.Favaro, L.C.de Oliveira, A.S.Barbosa, R.K.Salinas, R.F.de Souza, C.S.Farah, C.R.Guzzo.

ABSTRACT

Leptospira interrogans serovar Copenhageni is a human pathogen that causes leptospirosis, a worldwide zoonosis. The L. interrogans genome codes for a wide array of potential diguanylate cyclase (DGC) enzymes with characteristic GGDEF domains capable of synthesizing the cyclic dinucleotide c-di-GMP, known to regulate transitions between different cellular behavioral states in bacteria. Among such enzymes, LIC13137 (Lcd1), which has an N-terminal cGMP-specific phosphodiesterases, adenylyl cyclases, and FhlA (GAF) domain and a C-terminal GGDEF domain, is notable for having close orthologs present only in pathogenic Leptospira species. Although the function and structure of GGDEF and GAF domains have been studied extensively separately, little is known about enzymes with the GAF-GGDEF architecture. In this report, we address the question of how the GAF domain regulates the DGC activity of Lcd1. The full-length Lcd1 and its GAF domain form dimers in solution. The GAF domain binds specifically cAMP (K_Dof 0.24μM) and has an important role in the regulation of the DGC activity of the GGDEF domain. Lcd1 DGC activity is negligible in the absence of cAMP and is significantly enhanced in its presence (specific activity of 0.13s^-1). The crystal structure of the Lcd1 GAF domain in complex with cAMP provides valuable insights toward explaining its specificity for cAMP and pointing to possible mechanisms by which this cyclic nucleotide regulates the assembly of an active DGC enzyme.