Crystal structure of 1-deoxy-d-xylulose 5-phosphate reductoisomerase from the hyperthermophile Thermotoga maritima for insights into the coordination of conformational changes and an inhibitor binding

A Semipinacol Rearrangement Directed by an Enzymatic System Featuring Dual‐Function FAD‐Dependent Monooxygenase

“…[15][16][17] (Scheme 2 B,C). Both enzymes exhibit dual functionality by catalyzing isomerization followed by reduction at a single active site and require divalent metal ions for isomerization in addition to NAD(P)H. As proposed by Tyagi et al, the reduction is important for overcoming the unfavorable equilibrium state of the isomerization.…”

Structural and functional studies of mycobacterial IspD enzymes

“…If we use the domain definitions of Steinbacher et al (2003), this central domain also contains the residues of the active site. Comparison of the published structures of DXR shows that these domains are loosely coupled, sliding with respect to each other by essentially rigidbody motions (Henriksson et al, 2007;Takenoya et al, 2010). A simple yardstick, the distance between selected points in the N-and C-terminal domains (the C atoms of residues 47 and 339, respectively, in MtDXR), can be used to measure the degree of opening of the NADPH-binding site (Henriksson et al, 2007).…”

Mechanism and inhibition of 1-deoxy-d-xylulose-5-phosphate reductoisomerase

“…The values of K i /K i à vary from 4 to 10 for E. coli DXR [35,81,83] up to 225 for Synechocystis DXR [80], indicating that the favorability of the purported equilibrium depends on the enzyme's source. Based on these observations, the slow, tightbinding behavior of fosmidomycin was assumed for DXRs from Francisella tularensis [84], Thermotoga maritima [85], P. falciparum [86], and T. gondii [41]; by pre-incubating these enzymes with the inhibitor for 5-10 min prior to initiation of the reaction with DXP, the slow-onset phase was avoided, and therefore, the observed inhibition constants in these cases represent K i à (Table 3). Interestingly, fosmidomycin analogues with a reversed hydroxamic moiety (Fig.…”