Acta crystallographica. Section F, Structural biology communications最新文献

Immunoglobulin A (IgA) proteases are a group of bacterial-derived enzymes that selectivity hydrolyze human IgA in the hinge region that is unique to this immunoglobulin. Several IgA protease (IgAP) families have evolved this ability using both metalloprotease and serine protease chemical mechanisms. One family of metal-dependent IgAPs is the M26 family. This family can be grouped into two subfamilies based upon the presence or absence of a trypsin-like domain found N-terminal to the IgAP domain. The role of this domain in IgAP structure and function is poorly understood. Here, we present the first structural characterization of an M26 IgAP trypsin-like domain from Gemella haemolysans (GhTrp). These structural data demonstrate that the GhTrp domain possesses a trypsin-like fold but contains significant deviations in the surface-loop structure that is known to be coupled to protease selectivity. The lack of observable catalytic function coupled with the structural data suggest that this domain may exist in a pro-enzyme-like state that can potentially be activated when the domain is N-terminally proteolytically excised from the larger M26 IgAP structure.

Corrections are made to the article by Ando et al. [(2025), Acta Cryst. F81, 95-100].

Legionella pneumophila serogroup 1 is the primary causative agent of Legionnaires' disease, a rare but severe respiratory infection. While the fatality rate of Legionnaires' disease is low in the general population, it is more pronounced in vulnerable communities such as the immunocompromised. Thus, the development of new antimicrobials is of interest for use when existing antibiotics may not be applicable. Peptide deformylases (PDFs) have been under continued investigation as targets for novel antimicrobial compounds. PDF plays an essential role in protein synthesis, removing the N-terminal formyl group from new polypeptides, and is required for growth in most bacteria. Here, we report two crystal structures of L. pneumophila serogroup 1 PDF (LpPDF) bound to either Ni²⁺, an active state, or inhibited by actinonin and Zn²⁺; the structures were determined to 1.5 and 1.65 Å resolution, respectively, and were solved by the Seattle Structural Genomics Center for Infectious Disease (SSGCID). The SSGCID is charged with determining structures of biologically important proteins and molecules from human pathogens. As actinonin is an antimicrobial natural product that has been used as a reference compound in drug development, these structures will help support the ongoing drug-development process.

Photosynthesis is the largest-scale energy and material conversion process on Earth. The cytchrome (Cyt) b₆f complex plays a crucial role in photosynthesis. Under high-light conditions, cyclophilin 37 (CYP37) in Arabidopsis thaliana (AtCYP37) can interact with the PetA subunit of Cyt b₆f, thereby helping plants initiate photoprotection. Here, we purified, crystallized and determined a 1.95 Å resolution structure of AtCYP37. Overall, AtCYP37 consists of an N-terminal domain dominated by α-helices and a C-terminal domain mainly composed of β-strands and random coils. The structure shows significant similarity to those of Anabaena sp. CYPA and A. thaliana CYP38. Understanding the structure of AtCYP37 is significant as it may help to decipher how plants regulate photosynthesis and protect against high light damage, contributing to a broader understanding of plant photobiology and potentially guiding future research in improving plant stress tolerance.

Cellular deoxyuridine 5′-triphosphate nucleotidohydrolases (dUTPases) catalyze the hydrolysis of deoxyuridine triphosphate (dUTP) to deoxyuridine monophosphate (dUMP) and pyrophosphate (PP_i). dUTPase is an essential metabolic enzyme which maintains the homeostatic dTTP:dUTP ratio. As DNA polymerases are unable to distinguish between thymine and uracil during replication, the dTTP:dUTP ratio is essential for preventing the misincorporation of uracil into DNA. In the absence of dUTPase regulation of the dTTP:dUTP ratio, many DNA double-strand breaks are induced by DNA-repair enzymes, which may ultimately lead to cell death. Legionnaires' disease is a rare but severe respiratory infection caused primarily by Legionella pneumophila serogroup 1. Increased characterization of the L. pneumophila proteome is of interest for the development of new treatments. Many DNA metabolism proteins have yet to be characterized in L. pneumophila, including dUTPase. Here, we present analysis of two crystal structures of L. pneumophila dUTPase in its apo and dUMP-bound states, determined to 1.80 and 1.95 Å resolution, respectively. The structures were solved by the Seattle Structural Genomics Center for Infectious Disease (SSGCID) as part of their mission to determine structures of proteins and other molecules with an important biological role in human pathogens.

Mycobacterium tuberculosis is a Gram-positive bacillus that causes tuberculosis and is a leading cause of mortality worldwide. This disease is a growing health threat due to the occurrence of multidrug resistance. Mycolic acids are essential for generating cell walls and their modification is important to the virulence and persistence of M. tuberculosis. A family of S-adenosylmethionine-dependent mycolic acid synthases modify mycolic acids and represent promising drug targets. UmaA is currently the least-understood member of this family. This paper describes the crystal structure of UmaA. UmaA is a monomer composed of two domains: a structurally conserved SAM-binding domain and a variable substrate-binding auxiliary domain. Fortuitously, our structure contains a nitrate in the active site, a structural mimic of carbonate, which is a known general base in cyclopropane-adding synthases. Further investigation indicated that the structure of the N-terminus is highly flexible. Finally, we have identified S-adenosyl-N-decyl-aminoethyl as a promising potential inhibitor.

The methylerythritol phosphate (MEP) pathway is a metabolic pathway that produces the isoprenoids isopentyl pyrophosphate and dimethylallyl pyrophosphate. Notably, the MEP pathway is present in bacteria and not in mammals, which makes the enzymes of the MEP pathway attractive targets for the discovery of new anti-infective agents due to the reduced chances of off-target interactions leading to side effects. There are seven enzymes in the MEP pathway, the fifth of which is IspF. Crystal structures of Burkholderia pseudomallei IspF were determined with five different sulfonamide ligands bound. The sulfonamide-containing ligands were ethoxzolamide, acetazolamide, sulfapyridine and sulfamonomethoxine. The fifth bound ligand was a synthetic analog of acetazolamide. All ligands coordinated to the active-site Zn⁺² ion through the sulfonamide group, although sulfapyridine and sulfamonomethoxine, both of which are known antibacterial agents, possess similar binding interactions that are distinct from the other three sulfonamides. These structural data will aid in the discovery of new IspF inhibitors.

Neisseria gonorrhoeae, the causative agent of the human disease gonorrhea, is the second most common sexually transmitted pathogen in the United States. Gonorrhea has a significantly high morbidity rate due to the ability of N. gonorrhoeae to rapidly develop antibiotic resistance. In this paper, crystal structures of tryptophanyl-tRNA synthetase (TrpRS) from N. gonorrhoeae (NgTrpRS) were determined in both its apo form and in complex with tryptophan. The structures reveal conserved HIGH and KMSKS motifs critical for ATP binding and catalysis, and highlight conformational changes in the active site upon tryptophan binding, including a methionine flip and the rearrangement of hydrogen-bonding residues. Structural alignments with human TrpRS isoforms demonstrate significant differences between the bacterial and human cytosolic forms, particularly in their active sites. While NgTrpRS and human mitochondrial TrpRS share conserved catalytic residues that are essential for binding tryptophan and indolmycin, the cytosolic TrpRS contains substitutions that introduce steric hindrance, limiting the binding of indolmycin. These results provide insight for the development of inhibitors targeting bacterial TrpRS without affecting the human mitochondrial or cytosolic isoforms, contributing to efforts to combat antibiotic-resistant N. gonorrhoeae infections.