6CKL

N. meningitidis CMP-sialic acid synthetase in the presence of CMP and Neu5Ac2en

Summary for 6CKL

• Entry DOI: 10.2210/pdb6ckl/pdb
• Descriptor: N-acylneuraminate cytidylyltransferase, CYTIDINE-5'-MONOPHOSPHATE, CHLORIDE ION, ... (6 entities in total)
• Functional Keywords: polysaccharide synthesis, sialic acid-activator, cmp-transferase, transferase
• Biological source: Neisseria meningitidis
• Total number of polymer chains: 3
• Total formula weight: 77089.14

Authors

Matthews, M.M.,Fisher, A.J.,Chen, X. (deposition date: 2018-02-28, release date: 2019-03-06, Last modification date: 2023-10-04)

Primary citation

Matthews, M.M.,McArthur, J.B.,Li, Y.,Yu, H.,Chen, X.,Fisher, A.J.
Catalytic Cycle ofNeisseria meningitidisCMP-Sialic Acid Synthetase Illustrated by High-Resolution Protein Crystallography.
Biochemistry, 2019

PubMed Abstract: Cytidine 5'-monophosphate (CMP)-sialic acid synthetase (CSS) is an essential enzyme involved in the biosynthesis of carbohydrates and glycoconjugates containing sialic acids, a class of α-keto acids that are generally terminal key recognition residues by many proteins that play important biological and pathological roles. The CSS from (NmCSS) has been commonly used with other enzymes such as sialic acid aldolase and/or sialyltransferase in synthesizing a diverse array of compounds containing sialic acid or its naturally occurring and non-natural derivatives. To better understand its catalytic mechanism and substrate promiscuity, four NmCSS crystal structures trapped at various stages of the catalytic cycle with bound substrates, substrate analogues, and products have been obtained and are presented here. These structures suggest a mechanism for an "open" and "closed" conformational transition that occurs as sialic acid binds to the NmCSS/cytidine-5'-triphosphate (CTP) complex. The closed conformation positions critical residues to help facilitate the nucleophilic attack of sialic acid C2-OH to the α-phosphate of CTP, which is also aided by two observed divalent cations. Product formation drives the active site opening, promoting the release of products.

PubMed: 31583886
DOI: 10.1021/acs.biochem.9b00517

Experimental method

X-RAY DIFFRACTION (2.684 Å)