The enzyme 3-deoxy-manno-octulosonate cytidylyltransferase (CMP-KDO synthetase; CKS) catalyzes the activation of 3-deoxy-D-manno-octulosonate (or 2-keto-3-deoxy-manno-octonic acid; KDO) by forming CMP-KDO. The enzymes belong to cytidylyltransferase protein family being a part of GT-A clan that contains diverse glycosyltransferases that possess a Rossmann like fold. KDO is an essential component of lipopolysaccharides (LPS) in Gram-negative bacteria. Incorporation of KDO into LPS requires its activation by 3-deoxy-manno-octulosonate CKS. The Yesinia pestis enzyme coded by kdsB gene is 77% identical to its E.coli homolog. Two isozymes of CKS have been found in Escherichia coli. One of them, named L-CKS, is encoded by the kdsB gene and participates in the biosynthesis of LPS. The other isozyme, K-CKS, is encoded by the kpsU gene and is involved in capsule expression. CKS is unique to Gram-negative bacteria and is absent from mammalian cells. Therefore, CKS is an attractive target for the development of antibacterial agents.