1JBV

FPGS-AMPPCP complex

Summary for 1JBV

• Entry DOI: 10.2210/pdb1jbv/pdb
• Related: 1FGS 1JBW
• Descriptor: FOLYLPOLYGLUTAMATE SYNTHASE, MAGNESIUM ION, PHOSPHOMETHYLPHOSPHONIC ACID ADENYLATE ESTER, ... (4 entities in total)
• Functional Keywords: fpgs amppcp complex, ligase
• Biological source: Lactobacillus casei
• Total number of polymer chains: 1
• Total formula weight: 47250.83

Authors

Sun, X.,Cross, J.A.,Bognar, A.L.,Baker, E.N.,Smith, C.A. (deposition date: 2001-06-06, release date: 2001-09-19, Last modification date: 2023-11-15)

Primary citation

Sun, X.,Cross, J.A.,Bognar, A.L.,Baker, E.N.,Smith, C.A.
Folate-binding triggers the activation of folylpolyglutamate synthetase.
J.Mol.Biol., 310:1067-1078, 2001

PubMed Abstract: Folic acid is an essential vitamin for normal cell growth, primarily through its central role in one-carbon metabolism. Folate analogs (antifolates) are targeted at the same reactions and are widely used as therapeutic drugs for cancer and bacterial infections. Effective retention of folates in cells and the efficacy of antifolate drugs both depend upon the addition of a polyglutamate tail to the folate or antifolate molecule by the enzyme folylpolyglutamate synthetase (FPGS). The reaction mechanism involves the ATP-dependent activation of the free carboxylate group on the folate molecule to give an acyl phosphate intermediate, followed by attack by the incoming L-glutamate substrate. FPGS shares a number of structural and mechanistic details with the bacterial cell wall ligases MurD, MurE and MurF, and these enzymes, along with FPGS, form a subfamily of the ADP-forming amide bond ligase family. High-resolution crystallographic analyses of binary and ternary complexes of Lactobacillus casei FPGS reveal that binding of the first substrate (ATP) is not sufficient to generate an active enzyme. However, binding of folate as the second substrate triggers a large conformational change that activates FPGS and allows the enzyme to adopt a form that is then able to bind the third substrate, L-glutamate, and effect the addition of a polyglutamate tail to the folate.

PubMed: 11501996
DOI: 10.1006/jmbi.2001.4815

Experimental method

X-RAY DIFFRACTION (1.95 Å)