{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T17:42:58Z","timestamp":1781631778015,"version":"3.54.5"},"reference-count":41,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2007,10,17]],"date-time":"2007-10-17T00:00:00Z","timestamp":1192579200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecular Microbiology"],"published-print":{"date-parts":[[2007,11]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Human leishmaniasis is a major public health problem in many countries, but chemotherapy is in an unsatisfactory state. <jats:italic>Leishmania major<\/jats:italic> phosphodiesterases (LmjPDEs) have been shown to play important roles in cell proliferation and apoptosis of the parasite. Thus LmjPDE inhibitors may potentially represent a novel class of drugs for the treatment of leishmaniasis. Reported here are the kinetic characterization of the LmjPDEB1 catalytic domain and its crystal structure as a complex with 3\u2010isobutyl\u20101\u2010methylxanthine (IBMX) at 1.55 \u00c5 resolution. The structure of LmjPDEB1 is similar to that of human PDEs. IBMX stacks against the conserved phenylalanine and forms a hydrogen bond with the invariant glutamine, in a pattern common to most inhibitors bound to human PDEs. However, an extensive structural comparison reveals subtle, but significant differences between the active sites of LmjPDEB1 and human PDEs. In addition, a pocket next to the inhibitor binding site is found to be unique to LmjPDEB1. This pocket is isolated by two gating residues in human PDE families, but constitutes a natural expansion of the inhibitor binding pocket in LmjPDEB1. The structure particularity might be useful for the development of parasite\u2010selective inhibitors for the treatment of leishmaniasis.<\/jats:p>","DOI":"10.1111\/j.1365-2958.2007.05976.x","type":"journal-article","created":{"date-parts":[[2007,10,18]],"date-time":"2007-10-18T12:54:31Z","timestamp":1192712071000},"page":"1029-1038","source":"Crossref","is-referenced-by-count":59,"title":["Crystal structure of the <i>Leishmania major<\/i> phosphodiesterase LmjPDEB1 and insight into the design of the parasite\u2010selective inhibitors"],"prefix":"10.1111","volume":"66","author":[{"given":"Huanchen","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zier","family":"Yan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Geng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Kunz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Seebeck","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hengming","family":"Ke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2007,10,17]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1099\/jmm.0.46841-0"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1124\/pr.58.3.5"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.2174\/138161206777698855"},{"key":"e_1_2_5_5_1","first-page":"905","article-title":"Crystallography 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