Matthew D. Zimmerman
University of Virginia
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Featured researches published by Matthew D. Zimmerman.
Molecular Immunology | 2012
Karolina A. Majorek; Przemyslaw J. Porebski; Arjun Dayal; Matthew D. Zimmerman; Kamila Jablonska; Alan J. Stewart; Maksymilian Chruszcz; Wladek Minor
Serum albumin (SA) is the most abundant plasma protein in mammals. SA is a multifunctional protein with extraordinary ligand binding capacity, making it a transporter molecule for a diverse range of metabolites, drugs, nutrients, metals and other molecules. Due to its ligand binding properties, albumins have wide clinical, pharmaceutical, and biochemical applications. Albumins are also allergenic, and exhibit a high degree of cross-reactivity due to significant sequence and structure similarity of SAs from different organisms. Here we present crystal structures of albumins from cattle (BSA), horse (ESA) and rabbit (RSA) sera. The structural data are correlated with the results of immunological studies of SAs. We also analyze the conservation or divergence of structures and sequences of SAs in the context of their potential allergenicity and cross-reactivity. In addition, we identified a previously uncharacterized ligand binding site in the structure of RSA, and calcium binding sites in the structure of BSA, which is the first serum albumin structure to contain metal ions.
Journal of Biological Chemistry | 2008
Natalia Beloglazova; Greg Brown; Matthew D. Zimmerman; Michael Proudfoot; Kira S. Makarova; Marina Kudritska; Samvel Kochinyan; Shuren Wang; Maksymilian Chruszcz; Wladek Minor; Eugene V. Koonin; A. Edwards; Alexei Savchenko; Alexander Yakunin
Clustered regularly interspaced short palindromic repeats (CRISPRs) together with the associated CAS proteins protect microbial cells from invasion by foreign genetic elements using presently unknown molecular mechanisms. All CRISPR systems contain proteins of the CAS2 family, suggesting that these uncharacterized proteins play a central role in this process. Here we show that the CAS2 proteins represent a novel family of endoribonucleases. Six purified CAS2 proteins from diverse organisms cleaved single-stranded RNAs preferentially within U-rich regions. A representative CAS2 enzyme, SSO1404 from Sulfolobus solfataricus, cleaved the phosphodiester linkage on the 3′-side and generated 5′-phosphate- and 3′-hydroxyl-terminated oligonucleotides. The crystal structure of SSO1404 was solved at 1.6Å resolution revealing the first ribonuclease with a ferredoxin-like fold. Mutagenesis of SSO1404 identified six residues (Tyr-9, Asp-10, Arg-17, Arg-19, Arg-31, and Phe-37) that are important for enzymatic activity and suggested that Asp-10 might be the principal catalytic residue. Thus, CAS2 proteins are sequence-specific endoribonucleases, and we propose that their role in the CRISPR-mediated anti-phage defense might involve degradation of phage or cellular mRNAs.
Journal of Structural and Functional Genomics | 2011
Margaret Gabanyi; Paul D. Adams; Konstantin Arnold; Lorenza Bordoli; Lester Carter; Judith Flippen-Andersen; Lida Gifford; Juergen Haas; Andrei Kouranov; William A. McLaughlin; David Micallef; Wladek Minor; Raship Shah; Torsten Schwede; Yi-Ping Tao; John D. Westbrook; Matthew D. Zimmerman; Helen M. Berman
The Protein Structure Initiative’s Structural Biology Knowledgebase (SBKB, URL: http://sbkb.org) is an open web resource designed to turn the products of the structural genomics and structural biology efforts into knowledge that can be used by the biological community to understand living systems and disease. Here we will present examples on how to use the SBKB to enable biological research. For example, a protein sequence or Protein Data Bank (PDB) structure ID search will provide a list of related protein structures in the PDB, associated biological descriptions (annotations), homology models, structural genomics protein target status, experimental protocols, and the ability to order available DNA clones from the PSI:Biology-Materials Repository. A text search will find publication and technology reports resulting from the PSI’s high-throughput research efforts. Web tools that aid in research, including a system that accepts protein structure requests from the community, will also be described. Created in collaboration with the Nature Publishing Group, the Structural Biology Knowledgebase monthly update also provides a research library, editorials about new research advances, news, and an events calendar to present a broader view of structural genomics and structural biology.
Protein Science | 2008
Maksymilian Chruszcz; Wojciech Potrzebowski; Matthew D. Zimmerman; Marek Grabowski; Heping Zheng; Piotr Lasota; Wladek Minor
A nonredundant set of 9081 protein crystal structures in the Protein Data Bank was used to examine the solvent content, the number of polypeptide chains, and the oligomeric states of proteins in crystals as a function of crystal symmetry (as classified by crystal systems and space groups). It was found that there is a correlation between solvent content and crystal symmetry. Surprisingly, proteins crystallizing in lower symmetry systems have lower solvent content compared to those crystallizing in higher symmetry systems. Nevertheless, there is no universal correlation between solvent content and preferences of macromolecules to crystallize in certain space groups. Crystal symmetry as a function of oligomeric state was examined, where trimers, tetramers, and hexamers were found to prefer to crystallize in systems where the oligomer symmetry could be incorporated in the crystal symmetry. Our analysis also shows that the frequency distribution within the enantiomorphous pairs of space groups does not differ significantly, in contrast to previous reports.
Protein Science | 2010
Pawel Sledz; Heping Zheng; Krzysztof Murzyn; Maksymilian Chruszcz; Matthew D. Zimmerman; Mahendra D. Chordia; Andrzej Joachimiak; Wladek Minor
Surface lysine methylation (SLM) is a technique for improving the rate of success of protein crystallization by chemically methylating lysine residues. The exact mechanism by which SLM enhances crystallization is still not clear. To study these mechanisms, and to analyze the conditions where SLM will provide the optimal benefits for rescuing failed crystallization experiments, we compared 40 protein structures containing N,N‐dimethyl‐lysine (dmLys) to a nonredundant set of 18,972 nonmethylated structures from the PDB. By measuring the relative frequency of intermolecular contacts (where contacts are defined as interactions between the residues in proximity with a distance of 3.5 Å or less) of basic residues in the methylated versus nonmethylated sets, dmLys‐Glu contacts are seen more frequently than Lys‐Glu contacts. Based on observation of the 10 proteins with both native and methylated structures, we propose that the increased rate of contact for dmLys‐Glu is due to both a slight increase in the number of amine‐carboxyl H‐bonds and to the formation of methyl CH···O interactions. By comparing the relative contact frequencies of dmLys with other residues, the mechanism by which methylation of lysines improves the formation of crystal contacts appears to be similar to that of Lys to Arg mutation. Moreover, analysis of methylated structures with the surface entropy reduction (SER) prediction server suggests that in many cases SLM of predicted SER sites may contribute to improved crystallization. Thus, tools that analyze protein sequences and mark residues for SER mutation may identify proteins with good candidate sites for SLM.
Expert Opinion on Drug Discovery | 2015
Heping Zheng; Katarzyna B. Handing; Matthew D. Zimmerman; Ivan G. Shabalin; Steven C. Almo; Wladek Minor
Introduction: Macromolecular X-ray crystallography has been the primary methodology for determining the three-dimensional structures of proteins, nucleic acids and viruses. Structural information has paved the way for structure-guided drug discovery and laid the foundations for structural bioinformatics. However, X-ray crystallography still has a few fundamental limitations, some of which may be overcome and complemented using emerging methods and technologies in other areas of structural biology. Areas covered: This review describes how structural knowledge gained from X-ray crystallography has been used to advance other biophysical methods for structure determination (and vice versa). This article also covers current practices for integrating data generated by other biochemical and biophysical methods with those obtained from X-ray crystallography. Finally, the authors articulate their vision about how a combination of structural and biochemical/biophysical methods may improve our understanding of biological processes and interactions. Expert opinion: X-ray crystallography has been, and will continue to serve as, the central source of experimental structural biology data used in the discovery of new drugs. However, other structural biology techniques are useful not only to overcome the major limitation of X-ray crystallography, but also to provide complementary structural data that is useful in drug discovery. The use of recent advancements in biochemical, spectroscopy and bioinformatics methods may revolutionize drug discovery, albeit only when these data are combined and analyzed with effective data management systems. Accurate and complete data management is crucial for developing experimental procedures that are robust and reproducible.
Journal of Structural and Functional Genomics | 2010
Marcin Cymborowski; Maria M. Klimecka; Maksymilian Chruszcz; Matthew D. Zimmerman; Igor A. Shumilin; Dominika Borek; K. Lazarski; Andrzej Joachimiak; Zbyszek Otwinowski; Wayne F. Anderson; Wladek Minor
New protocols and instrumentation significantly boost the outcome of structural biology, which has resulted in significant growth in the number of deposited Protein Data Bank structures. However, even an enormous increase of the productivity of a single step of the structure determination process may not significantly shorten the time between clone and deposition or publication. For example, in a medium size laboratory equipped with the LabDB and HKL-3000 systems, we show that automation of some (and integration of all) steps of the X-ray structure determination pathway is critical for laboratory productivity. Moreover, we show that the lag period after which the impact of a technology change is observed is longer than expected.
Journal of Structural and Functional Genomics | 2016
Marek Grabowski; Ewa Niedzialkowska; Matthew D. Zimmerman; Wladek Minor
The period 2000–2015 brought the advent of high-throughput approaches to protein structure determination. With the overall funding on the order of
Journal of Molecular Biology | 2011
Maria M. Klimecka; Maksymilian Chruszcz; Jose Font; Tatiana Skarina; Igor A. Shumilin; Olena Onopryienko; Przemyslaw J. Porebski; Marcin Cymborowski; Matthew D. Zimmerman; Jeremy Hasseman; Ian J. Glomski; Lukasz Lebioda; Alexei Savchenko; A. Edwards; Wladek Minor
2 billion (in 2010 dollars), the structural genomics (SG) consortia established worldwide have developed pipelines for target selection, protein production, sample preparation, crystallization, and structure determination by X-ray crystallography and NMR. These efforts resulted in the determination of over 13,500 protein structures, mostly from unique protein families, and increased the structural coverage of the expanding protein universe. SG programs contributed over 4400 publications to the scientific literature. The NIH-funded Protein Structure Initiatives alone have produced over 2000 scientific publications, which to date have attracted more than 93,000 citations. Software and database developments that were necessary to handle high-throughput structure determination workflows have led to structures of better quality and improved integrity of the associated data. Organized and accessible data have a positive impact on the reproducibility of scientific experiments. Most of the experimental data generated by the SG centers are freely available to the community and has been utilized by scientists in various fields of research. SG projects have created, improved, streamlined, and validated many protocols for protein production and crystallization, data collection, and functional analysis, significantly benefiting biological and biomedical research.
Protein Science | 2007
Janusz J. Petkowski; Maksymilian Chruszcz; Matthew D. Zimmerman; Heping Zheng; Tatiana Skarina; Olena Onopriyenko; Marcin Cymborowski; Alexei Savchenko; A. Edwards; Wladek Minor
For the last decade, worldwide efforts for the treatment of anthrax infection have focused on developing effective vaccines. Patients that are already infected are still treated traditionally using different types of standard antimicrobial agents. The most popular are antibiotics such as tetracyclines and fluoroquinolones. While aminoglycosides appear to be less effective antimicrobial agents than other antibiotics, synthetic aminoglycosides have been shown to act as potent inhibitors of anthrax lethal factor and may have potential application as antitoxins. Here, we present a structural analysis of the BA2930 protein, a putative aminoglycoside acetyltransferase, which may be a component of the bacteriums aminoglycoside resistance mechanism. The determined structures revealed details of a fold characteristic only for one other protein structure in the Protein Data Bank, namely, YokD from Bacillus subtilis. Both BA2930 and YokD are members of the Antibiotic_NAT superfamily (PF02522). Sequential and structural analyses showed that residues conserved throughout the Antibiotic_NAT superfamily are responsible for the binding of the cofactor acetyl coenzyme A. The interaction of BA2930 with cofactors was characterized by both crystallographic and binding studies.